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362 entries « ‹ 1 of 19 › »

2019
1.	Franchet, Adrien; Niehus, Sebastian; Caravello, Gaetan; Ferrandon, Dominique: Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies. Nature Microbiology, 4 (4), pp. 645, 2019, ISBN: 2058-5276. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{Franchet2019, title = {Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies}, author = {Adrien Franchet and Sebastian Niehus and Gaetan Caravello and Dominique Ferrandon}, editor = {Nature Publishing Group}, url = {https://www.nature.com/articles/s41564-018-0344-y}, doi = {10.1038/s41564-018-0344-y}, isbn = {2058-5276}, year = {2019}, date = {2019-01-28}, journal = {Nature Microbiology}, volume = {4}, number = {4}, pages = {645}, abstract = {A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation. Close https://www.nature.com/articles/s41564-018-0344-y doi:10.1038/s41564-018-0344-y Close
2018
2.	Goto, Akira; Okado, Kiyoshi; Martins, Nelson; Cai, Hua; Barbier, Vincent; Lamiable, Olivier; Troxler, Laurent; Santiago, Estelle; Kuhn, Lauriane; Paik, Donggi; Silverman, Neal; Holleufer, Andreas; Hartmann, Rune; Liu, Jiyong; Peng, Tao; Hoffmann, Jules A; Meignin, Carine; Daeffler, Laurent; Imler, Jean-Luc: The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila. Immunity, (49), pp. 225-234, 2018. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{Goto2018, title = {The Kinase IKKβ Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila}, author = {Akira Goto and Kiyoshi Okado and Nelson Martins and Hua Cai and Vincent Barbier and Olivier Lamiable and Laurent Troxler and Estelle Santiago and Lauriane Kuhn and Donggi Paik and Neal Silverman and Andreas Holleufer and Rune Hartmann and Jiyong Liu and Tao Peng and Jules A. Hoffmann and Carine Meignin and Laurent Daeffler and Jean-Luc Imler}, editor = {Elsevier Inc.}, url = {https://doi.org/10.1016/j.immuni.2018.07.013}, doi = {j.immuni.2018.07.013}, year = {2018}, date = {2018-08-21}, journal = {Immunity}, number = {49}, pages = {225-234}, abstract = {Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Antiviral immunity in Drosophila involves RNA interference and poorly characterized inducible responses. Here, we showed that two components of the IMD pathway, the kinase dIKKβ and the transcription factor Relish, were required to control infection by two picorna-like viruses. We identified a set of genes induced by viral infection and regulated by dIKKβ and Relish, which included an ortholog of STING. We showed that dSTING participated in the control of infection by picorna-like viruses, acting upstream of dIKKβ to regulate expression of Nazo, an antiviral factor. Our data reveal an antiviral function for STING in an animal model devoid of interferons and suggest an evolutionarily ancient role for this molecule in antiviral immunity. Close https://doi.org/10.1016/j.immuni.2018.07.013 doi:j.immuni.2018.07.013 Close
3.	Haller, Samantha; Franchet, Adrien; Hakkim, A; Chen, J; Drenkard, E; Yu, S; Schirmeier, Steffi; Li, Zi; Martins, Nelson; Ausubel, FM; Liégeois, Samuel; Ferrandon, Dominique: Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization. EMBO Reports, 2018. (Type: Journal Article \| Links \| BibTeX) @article{S2018, title = {Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization}, author = {Samantha Haller and Adrien Franchet and A Hakkim and J Chen and E Drenkard and S Yu and Steffi Schirmeier and Zi Li and Nelson Martins and FM Ausubel and Samuel Liégeois and Dominique Ferrandon }, url = {http://embor.embopress.org/content/early/2018/03/09/embr.201744880}, doi = {10.15252/embr.201744880}, year = {2018}, date = {2018-03-09}, journal = {EMBO Reports}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://embor.embopress.org/content/early/2018/03/09/embr.201744880 doi:10.15252/embr.201744880 Close
4.	Issa, Najwa; Guillaumot, Nina; Lauret, Emilie; Matt, Nicolas; Scaeffer-Reiss, Christine; Dorsselaer, Alain Van; Reichhart, Jean-Marc; Veillard, Florian: The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway.. Molecular Cell, 69 (4), pp. 539-550, 2018, ISSN: 1097-2765. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{Issa2018, title = {The circulating protease Persephone is an immune sensor for microbial proteolytic activities upstream of the Drosophila Toll pathway.}, author = {Najwa Issa and Nina Guillaumot and Emilie Lauret and Nicolas Matt and Christine Scaeffer-Reiss and Alain Van Dorsselaer and Jean-Marc Reichhart and Florian Veillard}, url = {http://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30058-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1097276518300583%3Fshowall%3Dtrue}, doi = {10.1016/j.molcel.2018.01.029}, issn = {1097-2765}, year = {2018}, date = {2018-02-15}, journal = {Molecular Cell}, volume = {69}, number = {4}, pages = {539-550}, abstract = {Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns. Close http://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30058-3?_returnURL=htt[...] doi:10.1016/j.molcel.2018.01.029 Close
5.	Ferreira, Flávia Viana; Aguiar, Eric Roberto Guimarães Rocha; Olmo, Roenick Proveti; de Oliveira, Karla Pollyanna Vieira; Silva, Emanuele Guimarães; Sant'Anna, Maurício Roberto Viana; de Gontijo, Nelder Figueiredo; Kroon, Erna Geessien; Imler, Jean-Luc; Marques, João Trindade: The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis. PLoS Negl Trop Dis, 12 (6), pp. e0006569, 2018, ISSN: 1935-2735. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{ferreira_small_2018, title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis}, author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques}, doi = {10.1371/journal.pntd.0006569}, issn = {1935-2735}, year = {2018}, date = {2018-01-01}, journal = {PLoS Negl Trop Dis}, volume = {12}, number = {6}, pages = {e0006569}, abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens. Close doi:10.1371/journal.pntd.0006569 Close
2017
6.	Kuhn, Lauriane; Majzoub, Karim; Einhorn, Evelyne; Chicher, Johana; Pompon, Julien; Imler, Jean-Luc; Hammann, Philippe; Meignin, Carine: Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS. G3 (Bethesda), 2017, ISSN: 2160-1836. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{kuhn_definition_2017, title = {Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS}, author = { Lauriane Kuhn and Karim Majzoub and Evelyne Einhorn and Johana Chicher and Julien Pompon and Jean-Luc Imler and Philippe Hammann and Carine Meignin}, doi = {10.1534/g3.117.042564}, issn = {2160-1836}, year = {2017}, date = {2017-12-31}, journal = {G3 (Bethesda)}, abstract = {Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus. Close doi:10.1534/g3.117.042564 Close
7.	Patrnogic, Jelena; Leclerc, Vincent: The serine protease homolog spheroide is involved in sensing of pathogenic Gram-positive bacteria. PLoS One, 12 (12), 2017. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{Jelena2017, title = {The serine protease homolog spheroide is involved in sensing of pathogenic Gram-positive bacteria}, author = {Jelena Patrnogic and Vincent Leclerc}, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718610/}, doi = {10.1371/journal.pone.0188339}, year = {2017}, date = {2017-12-06}, journal = {PLoS One}, volume = {12}, number = {12}, abstract = {In Drosophila, recognition of pathogens such as Gram-positive bacteria and fungi triggers the activation of proteolytic cascades and the subsequent activation of the Toll pathway. This response can be achieved by either detection of pathogen associated molecular patterns or by sensing microbial proteolytic activities ("danger signals"). Previous data suggested that certain serine protease homologs (serine protease folds that lack an active catalytic triad) could be involved in the pathway. We generated a null mutant of the serine protease homolog spheroide (sphe). These mutant flies are susceptible to Enterococcus faecalis infection and unable to fully activate the Toll pathway. Sphe is required to activate the Toll pathway after challenge with pathogenic Gram-Positive bacteria. Sphe functions in the danger signal pathway, downstream or at the level of Persephone.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close In Drosophila, recognition of pathogens such as Gram-positive bacteria and fungi triggers the activation of proteolytic cascades and the subsequent activation of the Toll pathway. This response can be achieved by either detection of pathogen associated molecular patterns or by sensing microbial proteolytic activities ("danger signals"). Previous data suggested that certain serine protease homologs (serine protease folds that lack an active catalytic triad) could be involved in the pathway. We generated a null mutant of the serine protease homolog spheroide (sphe). These mutant flies are susceptible to Enterococcus faecalis infection and unable to fully activate the Toll pathway. Sphe is required to activate the Toll pathway after challenge with pathogenic Gram-Positive bacteria. Sphe functions in the danger signal pathway, downstream or at the level of Persephone. Close https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718610/ doi:10.1371/journal.pone.0188339 Close
8.	Volohonsky, Gloria; Hopp, Ann-Katrin; Saenger, Mélanie; Soichot, Julien; Scholze, Heidi; Boch, Jens; Blandin, Stéphanie A; Marois, Eric: Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae. PLOS Pathogens, 13 (1), pp. e1006113, 2017, ISSN: 1553-7374. (Type: Journal Article \| Links \| BibTeX) @article{volohonsky_transgenic_2017, title = {Transgenic Expression of the Anti-parasitic Factor TEP1 in the Malaria Mosquito Anopheles gambiae}, author = { Gloria Volohonsky and Ann-Katrin Hopp and Mélanie Saenger and Julien Soichot and Heidi Scholze and Jens Boch and Stéphanie A. Blandin and Eric Marois}, editor = {Vernick, Kenneth D}, url = {http://dx.plos.org/10.1371/journal.ppat.1006113}, doi = {10.1371/journal.ppat.1006113}, issn = {1553-7374}, year = {2017}, date = {2017-01-01}, urldate = {2017-02-01}, journal = {PLOS Pathogens}, volume = {13}, number = {1}, pages = {e1006113}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://dx.plos.org/10.1371/journal.ppat.1006113 doi:10.1371/journal.ppat.1006113 Close
9.	Mussabekova, Assel; Daeffler, Laurent; Imler, Jean-Luc: Innate and intrinsic antiviral immunity in Drosophila. Cell. Mol. Life Sci., 2017, ISSN: 1420-9071. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{mussabekova_innate_2017, title = {Innate and intrinsic antiviral immunity in Drosophila}, author = { Assel Mussabekova and Laurent Daeffler and Jean-Luc Imler}, doi = {10.1007/s00018-017-2453-9}, issn = {1420-9071}, year = {2017}, date = {2017-01-01}, journal = {Cell. Mol. Life Sci.}, abstract = {The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The fruit fly Drosophila melanogaster has been a valuable model to investigate the genetic mechanisms of innate immunity. Initially focused on the resistance to bacteria and fungi, these studies have been extended to include antiviral immunity over the last decade. Like all living organisms, insects are continually exposed to viruses and have developed efficient defense mechanisms. We review here our current understanding on antiviral host defense in fruit flies. A major antiviral defense in Drosophila is RNA interference, in particular the small interfering (si) RNA pathway. In addition, complex inducible responses and restriction factors contribute to the control of infections. Some of the genes involved in these pathways have been conserved through evolution, highlighting loci that may account for susceptibility to viral infections in humans. Other genes are not conserved and represent species-specific innovations. Close doi:10.1007/s00018-017-2453-9 Close
10.	Koltun, Bella; Shackelford, Eliza; Bonnay, François; Matt, Nicolas; Reichhart, Jean-Marc; Orian, Amir: The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity. The International Journal of Developmental Biology, 61 (3-4-5), pp. 319–327, 2017, ISSN: 0214-6282. (Type: Journal Article \| Links \| BibTeX) @article{koltun_sumo-targeted_2017, title = {The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity}, author = { Bella Koltun and Eliza Shackelford and François Bonnay and Nicolas Matt and Jean-Marc Reichhart and Amir Orian}, url = {http://www.intjdevbiol.com/paper.php?doi=160250ao}, doi = {10.1387/ijdb.160250ao}, issn = {0214-6282}, year = {2017}, date = {2017-01-01}, urldate = {2017-07-12}, journal = {The International Journal of Developmental Biology}, volume = {61}, number = {3-4-5}, pages = {319--327}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://www.intjdevbiol.com/paper.php?doi=160250ao doi:10.1387/ijdb.160250ao Close
11.	Chamy, Laure El; Matt, Nicolas; Reichhart, Jean-Marc: Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster. Microbiology Spectrum, 5 (1), 2017, ISSN: 2165-0497. (Type: Journal Article \| Links \| BibTeX) @article{Chamy2017, title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster}, author = { Laure El Chamy and Nicolas Matt and Jean-Marc Reichhart}, url = {http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0038-2016}, doi = {10.1128/microbiolspec.MCHD-0038-2016}, issn = {2165-0497}, year = {2017}, date = {2017-01-01}, urldate = {2017-07-12}, journal = {Microbiology Spectrum}, volume = {5}, number = {1}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://www.asmscience.org/content/journal/microbiolspec/10.1128/microbiolspec.MC[...] doi:10.1128/microbiolspec.MCHD-0038-2016 Close
12.	Gross, Lauriane; Vicens, Quentin; Einhorn, Evelyne; Noireterre, Audrey; Schaeffer, Laure; Kuhn, Lauriane; Imler, Jean-Luc; Eriani, Gilbert; Meignin, Carine; Martin, Franck: The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure. Nucleic Acids Research, 45 (15), pp. 8993–9004, 2017, ISSN: 1362-4962. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{gross_ires5utr_2017, title = {The IRES5'UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure}, author = { Lauriane Gross and Quentin Vicens and Evelyne Einhorn and Audrey Noireterre and Laure Schaeffer and Lauriane Kuhn and Jean-Luc Imler and Gilbert Eriani and Carine Meignin and Franck Martin}, doi = {10.1093/nar/gkx622}, issn = {1362-4962}, year = {2017}, date = {2017-01-01}, journal = {Nucleic Acids Research}, volume = {45}, number = {15}, pages = {8993--9004}, abstract = {Cricket paralysis virus (CrPV) is a dicistrovirus. Its positive-sense single-stranded RNA genome contains two internal ribosomal entry sites (IRESs). The 5' untranslated region (5'UTR) IRES5'UTR mediates translation of non-structural proteins encoded by ORF1 whereas the well-known intergenic region (IGR) IRESIGR is required for translation of structural proteins from open reading frame 2 in the late phase of infection. Concerted action of both IRES is essential for host translation shut-off and viral translation. IRESIGR has been extensively studied, in contrast the IRES5'UTR remains largely unexplored. Here, we define the minimal IRES element required for efficient translation initiation in drosophila S2 cell-free extracts. We show that IRES5'UTR promotes direct recruitment of the ribosome on the cognate viral AUG start codon without any scanning step, using a Hepatitis-C virus-related translation initiation mechanism. Mass spectrometry analysis revealed that IRES5'UTR recruits eukaryotic initiation factor 3, confirming that it belongs to type III class of IRES elements. Using Selective 2'-hydroxyl acylation analyzed by primer extension and DMS probing, we established a secondary structure model of 5'UTR and of the minimal IRES5'UTR. The IRES5'UTR contains a pseudoknot structure that is essential for proper folding and ribosome recruitment. Overall, our results pave the way for studies addressing the synergy and interplay between the two IRES from CrPV.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Cricket paralysis virus (CrPV) is a dicistrovirus. Its positive-sense single-stranded RNA genome contains two internal ribosomal entry sites (IRESs). The 5' untranslated region (5'UTR) IRES5'UTR mediates translation of non-structural proteins encoded by ORF1 whereas the well-known intergenic region (IGR) IRESIGR is required for translation of structural proteins from open reading frame 2 in the late phase of infection. Concerted action of both IRES is essential for host translation shut-off and viral translation. IRESIGR has been extensively studied, in contrast the IRES5'UTR remains largely unexplored. Here, we define the minimal IRES element required for efficient translation initiation in drosophila S2 cell-free extracts. We show that IRES5'UTR promotes direct recruitment of the ribosome on the cognate viral AUG start codon without any scanning step, using a Hepatitis-C virus-related translation initiation mechanism. Mass spectrometry analysis revealed that IRES5'UTR recruits eukaryotic initiation factor 3, confirming that it belongs to type III class of IRES elements. Using Selective 2'-hydroxyl acylation analyzed by primer extension and DMS probing, we established a secondary structure model of 5'UTR and of the minimal IRES5'UTR. The IRES5'UTR contains a pseudoknot structure that is essential for proper folding and ribosome recruitment. Overall, our results pave the way for studies addressing the synergy and interplay between the two IRES from CrPV. Close doi:10.1093/nar/gkx622 Close
2016
13.	Lee, Kwang-Zin; Lestradet, Matthieu; Socha, Catherine; Schirmeier, Stefanie; Schmitz, Antonin; Spenlé, Caroline; Lefebvre, Olivier; Keime, Céline; Yamba, Wennida M.; Bou Aoun, Richard; Liegeois, Samuel; Schwab, Yannick; Simon-Assmann, Patricia; Dalle, Frédéric; Ferrandon, Dominique: Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack. Cell Host & Microbe, 2016, ISSN: 1931-3128. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{Lee2016, title = {Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack}, author = { Kwang-Zin Lee and Matthieu Lestradet and Catherine Socha and Stefanie Schirmeier and Antonin Schmitz and Caroline Spenlé and Olivier Lefebvre and Céline Keime and Wennida M. Yamba and Richard Bou Aoun and Samuel Liegeois and Yannick Schwab and Patricia Simon-Assmann and Frédéric Dalle and Dominique Ferrandon}, editor = {L. Abate}, url = {http://www.sciencedirect.com/science/article/pii/S193131281630436X}, doi = {10.1016/j.chom.2016.10.010}, issn = {1931-3128}, year = {2016}, date = {2016-11-23}, urldate = {2016-11-25}, journal = {Cell Host & Microbe}, abstract = {Summary Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Summary Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals. Close http://www.sciencedirect.com/science/article/pii/S193131281630436X doi:10.1016/j.chom.2016.10.010 Close
14.	Ehrhardt, Katharina; Deregnaucourt, Christiane; Goetz, Alice-Anne; Tzanova, Tzvetomira; Gallo, Valentina; Arese, Paolo; Pradines, Bruno; Adjalley, Sophie H; Bagrel, Denyse; Blandin, Stephanie A; Lanzer, Michael; Davioud-Charvet, Elisabeth: The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites. Antimicrob. Agents Chemother., 60 (9), pp. 5146-5158 , 2016, ISSN: 1098-6596. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{ehrhardt_redox-cycler_2016, title = {The redox-cycler plasmodione is a fast acting antimalarial lead compound with pronounced activity against sexual and early asexual blood-stage parasites}, author = { Katharina Ehrhardt and Christiane Deregnaucourt and Alice-Anne Goetz and Tzvetomira Tzanova and Valentina Gallo and Paolo Arese and Bruno Pradines and Sophie H. Adjalley and Denyse Bagrel and Stephanie A. Blandin and Michael Lanzer and Elisabeth Davioud-Charvet}, url = {http://aac.asm.org/content/60/9/5146}, doi = {10.1128/AAC.02975-15}, issn = {1098-6596}, year = {2016}, date = {2016-09-01}, journal = {Antimicrob. Agents Chemother.}, volume = {60}, number = {9}, pages = { 5146-5158 }, abstract = {Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox-cyclers - a strategy that is broadly recognized for the development of new antimalarial agents. Here, we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intra-erythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common resistance mechanisms to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a fast killing speed as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that it is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent in vitro and in vivo activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox-cyclers - a strategy that is broadly recognized for the development of new antimalarial agents. Here, we report a detailed parasitological characterization of the in vitro activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intra-erythrocytic stages of the human malaria parasite Plasmodium falciparum We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intra-erythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common resistance mechanisms to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a fast killing speed as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that it is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents. Close http://aac.asm.org/content/60/9/5146 doi:10.1128/AAC.02975-15 Close
15.	Paro, Simona; Imler, Jean-Luc: Encyclopedia of Immunobiology. Ratcliffe, M (Ed.): 1 , Chapter “Immunity in insects”, pp. 454-461, Elsevier, 2016. (Type: Book Chapter \| BibTeX) @inbook{Paro0000, title = {Encyclopedia of Immunobiology}, author = {Simona Paro and Jean-Luc Imler}, editor = {M. Ratcliffe}, year = {2016}, date = {2016-08-01}, volume = {1}, pages = {454-461}, publisher = {Elsevier}, chapter = {“Immunity in insects”}, keywords = {}, pubstate = {published}, tppubtype = {inbook} } Close
16.	Boujard, Daniel; Leclerc, Vincent; Vincent, Stéphane: Biologie du développement. Editions Dunod, 2016, ISBN: 978-2-10-072085-9. (Type: Book \| Abstract \| Links \| BibTeX) @book{leclerc2016, title = {Biologie du développement}, author = {Daniel Boujard and Vincent Leclerc and Stéphane Vincent}, editor = {Editions Dunod}, url = {https://www.dunod.com/sciences-techniques/biologie-du-developpement}, isbn = {978-2-10-072085-9}, year = {2016}, date = {2016-06-01}, booktitle = {Biologie du développement}, pages = {304}, edition = {Editions Dunod}, crossref = {EAN: 9782100720859}, abstract = {La biologie du développement étudie les phénomènes qui permettent le passage d’un œuf à un organisme adulte. Cette discipline a beaucoup évolué ces dernières années avec l'essor des nouvelles techniques d’imagerie in vivo, des « omiques » et des techniques de transgénèse. Aux progrès technologiques s’ajoutent les avancées importantes en génétique et épigénétique, tout cela permettant d’avoir aujourd’hui une vision beaucoup plus intégrée des mécanismes fondamentaux de la biologie du développement. L’objectif de l’ouvrage est de fournir une vision synthétique et moderne de la discipline tout en montrant son lien avec la biologie cellulaire, la génétique, la physiologie et la médecine. Les principaux modèles, historiques ou émergents, sont présentés puis les grandes étapes du développement sont détaillées en s’appuyant sur les données les plus récentes. Un chapitre aborde l’importance de l’apport de la biologie du développement dans la compréhension de nombreuses pathologies, dont le cancer.}, keywords = {}, pubstate = {published}, tppubtype = {book} } Close La biologie du développement étudie les phénomènes qui permettent le passage d’un œuf à un organisme adulte. Cette discipline a beaucoup évolué ces dernières années avec l'essor des nouvelles techniques d’imagerie in vivo, des « omiques » et des techniques de transgénèse. Aux progrès technologiques s’ajoutent les avancées importantes en génétique et épigénétique, tout cela permettant d’avoir aujourd’hui une vision beaucoup plus intégrée des mécanismes fondamentaux de la biologie du développement. L’objectif de l’ouvrage est de fournir une vision synthétique et moderne de la discipline tout en montrant son lien avec la biologie cellulaire, la génétique, la physiologie et la médecine. Les principaux modèles, historiques ou émergents, sont présentés puis les grandes étapes du développement sont détaillées en s’appuyant sur les données les plus récentes. Un chapitre aborde l’importance de l’apport de la biologie du développement dans la compréhension de nombreuses pathologies, dont le cancer. Close https://www.dunod.com/sciences-techniques/biologie-du-developpement Close
17.	Lamiable, Olivier; Kellenberger, Christine; Kemp, Cordula; Troxler, Laurent; Pelte, Nadège; Boutros, Michael; Marques, Joao Trindade; Daeffler, Laurent; Hoffmann, Jules A; Roussel, Alain; Imler, Jean-Luc: Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila. PNAS, 113 (3), pp. 698–703, 2016, ISSN: 0027-8424, 1091-6490. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{lamiable_cytokine_2016, title = {Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila}, author = { Olivier Lamiable and Christine Kellenberger and Cordula Kemp and Laurent Troxler and Nadège Pelte and Michael Boutros and Joao Trindade Marques and Laurent Daeffler and Jules A. Hoffmann and Alain Roussel and Jean-Luc Imler}, url = {http://www.pnas.org/content/113/3/698.abstract}, doi = {10.1073/pnas.1516122113}, issn = {0027-8424, 1091-6490}, year = {2016}, date = {2016-01-19}, urldate = {2016-01-07}, journal = {PNAS}, volume = {113}, number = {3}, pages = {698–703}, abstract = {Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response. Close http://www.pnas.org/content/113/3/698.abstract doi:10.1073/pnas.1516122113 Close
18.	Lamiable, Olivier; Arnold, Johan; da de Faria, Isaque Joao Silva; Olmo, Roenick Proveti; Bergami, Francesco; Meignin, Carine; Hoffmann, Jules A; Marques, Joao Trindade; Imler, Jean-Luc: Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity. J. Virol., 90 (11), pp. 5415–5426, 2016, ISSN: 0022-538X, 1098-5514. (Type: Journal Article \| Links \| BibTeX) @article{lamiable_analysis_2016, title = {Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity}, author = { Olivier Lamiable and Johan Arnold and Isaque Joao da Silva de Faria and Roenick Proveti Olmo and Francesco Bergami and Carine Meignin and Jules A. Hoffmann and Joao Trindade Marques and Jean-Luc Imler}, url = {http://jvi.asm.org/content/90/11/5415}, doi = {10.1128/JVI.00238-16}, issn = {0022-538X, 1098-5514}, year = {2016}, date = {2016-01-01}, urldate = {2016-06-05}, journal = {J. Virol.}, volume = {90}, number = {11}, pages = {5415--5426}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://jvi.asm.org/content/90/11/5415 doi:10.1128/JVI.00238-16 Close
19.	Marques, João T; Imler, Jean-Luc: The diversity of insect antiviral immunity: insights from viruses. Current Opinion in Microbiology, 32 , pp. 71–76, 2016, ISSN: 1369-5274. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{marques_diversity_2016, title = {The diversity of insect antiviral immunity: insights from viruses}, author = { João T Marques and Jean-Luc Imler}, url = {http://www.sciencedirect.com/science/article/pii/S1369527416300571}, doi = {10.1016/j.mib.2016.05.002}, issn = {1369-5274}, year = {2016}, date = {2016-01-01}, urldate = {2016-06-05}, journal = {Current Opinion in Microbiology}, volume = {32}, pages = {71--76}, abstract = {Insects represent over 70% of all animal species. Recent virome analyses reveal unprecedented genetic diversity of insect viruses, which appears to match that of their hosts. Thus, insect-virus interactions may provide information on a vast repertoire of antiviral immune mechanisms. Tapping into this diversity is challenging because of several constraints imposed by the uniqueness of each insect model. Nevertheless, it is clear that many conserved and divergent pathways participate in the control of viral infection in insects. Co-evolution between hosts and viruses favors the development of immune evasion mechanisms by the pathogen. Viral suppressors can offer unique perspective on host pathways and emphasize the importance of RNA interference, apoptosis, but also NF-κB pathways and translation control in insect antiviral immunity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Insects represent over 70% of all animal species. Recent virome analyses reveal unprecedented genetic diversity of insect viruses, which appears to match that of their hosts. Thus, insect-virus interactions may provide information on a vast repertoire of antiviral immune mechanisms. Tapping into this diversity is challenging because of several constraints imposed by the uniqueness of each insect model. Nevertheless, it is clear that many conserved and divergent pathways participate in the control of viral infection in insects. Co-evolution between hosts and viruses favors the development of immune evasion mechanisms by the pathogen. Viral suppressors can offer unique perspective on host pathways and emphasize the importance of RNA interference, apoptosis, but also NF-κB pathways and translation control in insect antiviral immunity. Close http://www.sciencedirect.com/science/article/pii/S1369527416300571 doi:10.1016/j.mib.2016.05.002 Close
20.	Martins, Nelson; Imler, Jean-Luc; Meignin, Carine: Discovery of novel targets for antivirals: learning from flies. Curr Opin Virol, 20 , pp. 64–70, 2016, ISSN: 1879-6265. (Type: Journal Article \| Abstract \| Links \| BibTeX) @article{martins_discovery_2016, title = {Discovery of novel targets for antivirals: learning from flies}, author = { Nelson Martins and Jean-Luc Imler and Carine Meignin}, url = {http://www.sciencedirect.com/science/article/pii/S1879625716301274}, doi = {10.1016/j.coviro.2016.09.005}, issn = {1879-6265}, year = {2016}, date = {2016-01-01}, journal = {Curr Opin Virol}, volume = {20}, pages = {64--70}, abstract = {Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Developing antiviral drugs is challenging due to the small number of targets in viruses, and the rapid evolution of viral genes. Animals have evolved a number of efficient antiviral defence mechanisms, which can serve as a source of inspiration for novel therapies. The genetically tractable insect Drosophila belongs to the most diverse group of animals. Genetic and transcriptomic analyses have recently identified Drosophila genes encoding viral restriction factors. Some of them represent evolutionary novelties and their characterization may provide hints for the design of directly acting antivirals. In addition, functional screens revealed conserved host factors required for efficient viral translation, such as the ribosomal protein RACK1 and the release factor Pelo. These proteins are promising candidates for host-targeted antivirals. Close http://www.sciencedirect.com/science/article/pii/S1879625716301274 doi:10.1016/j.coviro.2016.09.005 Close

362 entries « ‹ 1 of 19 › »

53 entries « ‹ 1 of 2 › »

2019
Journal Articles
53.	Franchet, Adrien; Niehus, Sebastian; Caravello, Gaetan; Ferrandon, Dominique Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies Journal Article Nature Microbiology, 4 (4), pp. 645, 2019, ISBN: 2058-5276. Abstract \| Links \| BibTeX @article{Franchet2019, title = {Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies}, author = {Adrien Franchet and Sebastian Niehus and Gaetan Caravello and Dominique Ferrandon}, editor = {Nature Publishing Group}, url = {https://www.nature.com/articles/s41564-018-0344-y}, doi = {10.1038/s41564-018-0344-y}, isbn = {2058-5276}, year = {2019}, date = {2019-01-28}, journal = {Nature Microbiology}, volume = {4}, number = {4}, pages = {645}, abstract = {A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation. Close https://www.nature.com/articles/s41564-018-0344-y doi:10.1038/s41564-018-0344-y Close
2018
Journal Articles
52.	Haller, Samantha; Franchet, Adrien; Hakkim, A; Chen, J; Drenkard, E; Yu, S; Schirmeier, Steffi; Li, Zi; Martins, Nelson; Ausubel, FM; Liégeois, Samuel; Ferrandon, Dominique Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization Journal Article EMBO Reports, 2018. Links \| BibTeX @article{S2018, title = {Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization}, author = {Samantha Haller and Adrien Franchet and A Hakkim and J Chen and E Drenkard and S Yu and Steffi Schirmeier and Zi Li and Nelson Martins and FM Ausubel and Samuel Liégeois and Dominique Ferrandon }, url = {http://embor.embopress.org/content/early/2018/03/09/embr.201744880}, doi = {10.15252/embr.201744880}, year = {2018}, date = {2018-03-09}, journal = {EMBO Reports}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://embor.embopress.org/content/early/2018/03/09/embr.201744880 doi:10.15252/embr.201744880 Close
2016
Journal Articles
51.	Lee, Kwang-Zin; Lestradet, Matthieu; Socha, Catherine; Schirmeier, Stefanie; Schmitz, Antonin; Spenlé, Caroline; Lefebvre, Olivier; Keime, Céline; Yamba, Wennida M.; Bou Aoun, Richard; Liegeois, Samuel; Schwab, Yannick; Simon-Assmann, Patricia; Dalle, Frédéric; Ferrandon, Dominique Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack Journal Article Cell Host & Microbe, 2016, ISSN: 1931-3128. Abstract \| Links \| BibTeX @article{Lee2016, title = {Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack}, author = { Kwang-Zin Lee and Matthieu Lestradet and Catherine Socha and Stefanie Schirmeier and Antonin Schmitz and Caroline Spenlé and Olivier Lefebvre and Céline Keime and Wennida M. Yamba and Richard Bou Aoun and Samuel Liegeois and Yannick Schwab and Patricia Simon-Assmann and Frédéric Dalle and Dominique Ferrandon}, editor = {L. Abate}, url = {http://www.sciencedirect.com/science/article/pii/S193131281630436X}, doi = {10.1016/j.chom.2016.10.010}, issn = {1931-3128}, year = {2016}, date = {2016-11-23}, urldate = {2016-11-25}, journal = {Cell Host & Microbe}, abstract = {Summary Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Summary Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals. Close http://www.sciencedirect.com/science/article/pii/S193131281630436X doi:10.1016/j.chom.2016.10.010 Close
2015
Journal Articles
50.	Brunke, Sascha; Quintin, Jessica; Kasper, Lydia; Jacobsen, Ilse D; Richter, Martin E; Hiller, Ekkehard; Schwarzmüller, Tobias; d'Enfert, Christophe; Kuchler, Karl; Rupp, Steffen; Hube, Bernhard; Ferrandon, Dominique Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts Journal Article Dis Model Mech, 8 (5), pp. 473–486, 2015, ISSN: 1754-8411. Abstract \| Links \| BibTeX @article{brunke_mice_2015b, title = {Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts}, author = { Sascha Brunke and Jessica Quintin and Lydia Kasper and Ilse D. Jacobsen and Martin E. Richter and Ekkehard Hiller and Tobias Schwarzmüller and Christophe d'Enfert and Karl Kuchler and Steffen Rupp and Bernhard Hube and Dominique Ferrandon}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415897/}, doi = {10.1242/dmm.019901}, issn = {1754-8411}, year = {2015}, date = {2015-01-01}, journal = {Dis Model Mech}, volume = {8}, number = {5}, pages = {473--486}, abstract = {Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host. Close http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415897/ doi:10.1242/dmm.019901 Close
2014
Journal Articles
49.	Amcheslavsky, Alla; Song, Wei; Li, Qi; Nie, Yingchao; Bragatto, Ivan; Ferrandon, Dominique; Perrimon, Norbert; Ip, Tony Y Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila Journal Article Cell Rep, 9 (1), pp. 32–39, 2014, ISSN: 2211-1247. Abstract \| Links \| BibTeX @article{amcheslavsky_enteroendocrine_2014b, title = {Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila}, author = { Alla Amcheslavsky and Wei Song and Qi Li and Yingchao Nie and Ivan Bragatto and Dominique Ferrandon and Norbert Perrimon and Y. Tony Ip}, doi = {10.1016/j.celrep.2014.08.052}, issn = {2211-1247}, year = {2014}, date = {2014-10-01}, journal = {Cell Rep}, volume = {9}, number = {1}, pages = {32--39}, abstract = {Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth. Close doi:10.1016/j.celrep.2014.08.052 Close
48.	Haller, Samantha; Limmer, Stefanie; Ferrandon, Dominique Assessing Pseudomonas virulence with a nonmammalian host: Drosophila melanogaster Journal Article Methods Mol. Biol., 1149 , pp. 723–740, 2014, ISSN: 1940-6029. Abstract \| Links \| BibTeX @article{haller_assessing_2014b, title = {Assessing Pseudomonas virulence with a nonmammalian host: Drosophila melanogaster}, author = { Samantha Haller and Stefanie Limmer and Dominique Ferrandon}, doi = {10.1007/978-1-4939-0473-0_56}, issn = {1940-6029}, year = {2014}, date = {2014-01-01}, journal = {Methods Mol. Biol.}, volume = {1149}, pages = {723--740}, abstract = {Drosophila melanogaster flies represent an interesting model to study host-pathogen interactions as: (1) they are cheap and easy to raise rapidly and do not bring up ethical issues, (2) available genetic tools are highly sophisticated, for instance allowing tissue-specific alteration of gene expression, e.g., of immune genes, (3) they have a relatively complex organization, with distinct digestive tract and body cavity in which local or systemic infections, respectively, take place, (4) a medium throughput can be achieved in genetic screens, for instance looking for Pseudomonas aeruginosa mutants with altered virulence. We present here the techniques used to investigate host-pathogen relationships, namely the two major models of infections as well as the relevant parameters used to monitor the infection (survival, bacterial titer, induction of host immune response).}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Drosophila melanogaster flies represent an interesting model to study host-pathogen interactions as: (1) they are cheap and easy to raise rapidly and do not bring up ethical issues, (2) available genetic tools are highly sophisticated, for instance allowing tissue-specific alteration of gene expression, e.g., of immune genes, (3) they have a relatively complex organization, with distinct digestive tract and body cavity in which local or systemic infections, respectively, take place, (4) a medium throughput can be achieved in genetic screens, for instance looking for Pseudomonas aeruginosa mutants with altered virulence. We present here the techniques used to investigate host-pathogen relationships, namely the two major models of infections as well as the relevant parameters used to monitor the infection (survival, bacterial titer, induction of host immune response). Close doi:10.1007/978-1-4939-0473-0_56 Close
47.	Schwarzmüller, Tobias; Ma, Biao; Hiller, Ekkehard; Istel, Fabian; Tscherner, Michael; Brunke, Sascha; Ames, Lauren; Firon, Arnaud; Green, Brian; Cabral, Vitor; Marcet-Houben, Marina; Jacobsen, Ilse D; Quintin, Jessica; Seider, Katja; Frohner, Ingrid; Glaser, Walter; Jungwirth, Helmut; Bachellier-Bassi, Sophie; Chauvel, Murielle; Zeidler, Ute; Ferrandon, Dominique; Gabaldón, Toni; Hube, Bernhard; d'Enfert, Christophe; Rupp, Steffen; Cormack, Brendan; Haynes, Ken; Kuchler, Karl Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes Journal Article PLoS Pathog., 10 (6), pp. e1004211, 2014, ISSN: 1553-7374. Abstract \| Links \| BibTeX @article{schwarzmuller_systematic_2014b, title = {Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes}, author = { Tobias Schwarzmüller and Biao Ma and Ekkehard Hiller and Fabian Istel and Michael Tscherner and Sascha Brunke and Lauren Ames and Arnaud Firon and Brian Green and Vitor Cabral and Marina Marcet-Houben and Ilse D. Jacobsen and Jessica Quintin and Katja Seider and Ingrid Frohner and Walter Glaser and Helmut Jungwirth and Sophie Bachellier-Bassi and Murielle Chauvel and Ute Zeidler and Dominique Ferrandon and Toni Gabaldón and Bernhard Hube and Christophe d'Enfert and Steffen Rupp and Brendan Cormack and Ken Haynes and Karl Kuchler}, doi = {10.1371/journal.ppat.1004211}, issn = {1553-7374}, year = {2014}, date = {2014-01-01}, journal = {PLoS Pathog.}, volume = {10}, number = {6}, pages = {e1004211}, abstract = {The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes. Close doi:10.1371/journal.ppat.1004211 Close
46.	Lestradet, Matthieu; Lee, Kwan Zin; Ferrandon, Dominique Drosophila as a model for intestinal infections Journal Article Methods Mol Biol, 1197 , pp. 11–40, 2014, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). Abstract \| Links \| BibTeX @article{lestradet_drosophila_2014b, title = {Drosophila as a model for intestinal infections}, author = { Matthieu Lestradet and Kwan Zin Lee and Dominique Ferrandon}, doi = {10.1007/978-1-4939-1261-2_2}, issn = {1940-6029 (Electronic) 1064-3745 (Linking)}, year = {2014}, date = {2014-01-01}, journal = {Methods Mol Biol}, volume = {1197}, pages = {11--40}, abstract = {Drosophila melanogaster is a powerful model to study infections thanks to the power of its genetics and knowledge on its biology accumulated for over a century. While the systemic humoral immune response against invading microbes has been intensively studied in the past two decades, the study of intestinal infections is more recent. Here, we present the methods that are currently in use to probe various aspects of the host-pathogen interactions between Drosophila and ingested microbes, with an emphasis on the study of the midgut epithelium, which constitutes the major interface between the organism and the microbe-rich ingested food.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Drosophila melanogaster is a powerful model to study infections thanks to the power of its genetics and knowledge on its biology accumulated for over a century. While the systemic humoral immune response against invading microbes has been intensively studied in the past two decades, the study of intestinal infections is more recent. Here, we present the methods that are currently in use to probe various aspects of the host-pathogen interactions between Drosophila and ingested microbes, with an emphasis on the study of the midgut epithelium, which constitutes the major interface between the organism and the microbe-rich ingested food. Close doi:10.1007/978-1-4939-1261-2_2 Close
2013
Journal Articles
45.	Quintin, Jessica; Asmar, Joelle; Matskevich, Alexey A; Lafarge, Marie-Céline; Ferrandon, Dominique The Drosophila Toll pathway controls but does not clear Candida glabrata infections Journal Article J. Immunol., 190 (6), pp. 2818–2827, 2013, ISSN: 1550-6606. Abstract \| Links \| BibTeX @article{quintin_drosophila_2013b, title = {The Drosophila Toll pathway controls but does not clear Candida glabrata infections}, author = { Jessica Quintin and Joelle Asmar and Alexey A. Matskevich and Marie-Céline Lafarge and Dominique Ferrandon}, doi = {10.4049/jimmunol.1201861}, issn = {1550-6606}, year = {2013}, date = {2013-03-01}, journal = {J. Immunol.}, volume = {190}, number = {6}, pages = {2818--2827}, abstract = {The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The pathogenicity of Candida glabrata to patients remains poorly understood for lack of convenient animal models to screen large numbers of mutants for altered virulence. In this study, we explore the minihost model Drosophila melanogaster from the dual perspective of host and pathogen. As in vertebrates, wild-type flies contain C. glabrata systemic infections yet are unable to kill the injected yeasts. As for other fungal infections in Drosophila, the Toll pathway restrains C. glabrata proliferation. Persistent C. glabrata yeasts in wild-type flies do not appear to be able to take shelter in hemocytes from the action of the Toll pathway, the effectors of which remain to be identified. Toll pathway mutant flies succumb to injected C. glabrata. In this immunosuppressed background, cellular defenses provide a residual level of protection. Although both the Gram-negative binding protein 3 pattern recognition receptor and the Persephone protease-dependent detection pathway are required for Toll pathway activation by C. glabrata, only GNBP3, and not psh mutants, are susceptible to the infection. Both Candida albicans and C. glabrata are restrained by the Toll pathway, yet the comparative study of phenoloxidase activation reveals a differential activity of the Toll pathway against these two fungal pathogens. Finally, we establish that the high-osmolarity glycerol pathway and yapsins are required for virulence of C. glabrata in this model. Unexpectedly, yapsins do not appear to be required to counteract the cellular immune response but are needed for the colonization of the wild-type host. Close doi:10.4049/jimmunol.1201861 Close
44.	Ferrandon, Dominique The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience Journal Article Curr. Opin. Immunol., 25 (1), pp. 59–70, 2013, ISSN: 1879-0372. Abstract \| Links \| BibTeX @article{ferrandon_complementary_2013b, title = {The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience}, author = { Dominique Ferrandon}, doi = {10.1016/j.coi.2012.11.008}, issn = {1879-0372}, year = {2013}, date = {2013-02-01}, journal = {Curr. Opin. Immunol.}, volume = {25}, number = {1}, pages = {59--70}, abstract = {Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs).}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Significant advances have been made in our understanding of the host defense against microbial infections taking place at frontier epithelia of Drosophila flies. Immune deficiency (IMD), the major NF-κB immune response pathway induced in these epithelia, displays remarkable adaptations in its activation and regulation in the respiratory and digestive tract. The host defense against ingested pathogens is not limited to resistance, that is, the immune response. It also involves resilience, the capacity of the host to endure and repair damages inflicted by pathogens or the host's own immune response. For instance, enterocytes damaged by pathogens, the microbiota of aging flies, or host-derived reactive oxygen species (ROS), are replaced under the control of multiple pathways by the compensatory proliferation of intestinal stem cells (ISCs). Close doi:10.1016/j.coi.2012.11.008 Close
43.	Ayyaz, Arshad; Giammarinaro, Philippe; Liégeois, Samuel; Lestradet, Matthieu; Ferrandon, Dominique A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus Journal Article Immunobiology, 218 (4), pp. 635–644, 2013, ISSN: 1878-3279. Abstract \| Links \| BibTeX @article{ayyaz_negative_2013b, title = {A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus}, author = { Arshad Ayyaz and Philippe Giammarinaro and Samuel Liégeois and Matthieu Lestradet and Dominique Ferrandon}, doi = {10.1016/j.imbio.2012.07.027}, issn = {1878-3279}, year = {2013}, date = {2013-01-01}, journal = {Immunobiology}, volume = {218}, number = {4}, pages = {635--644}, abstract = {Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Drosophila melanogaster is a useful model to investigate mucosal immunity. The immune response to intestinal infections is mediated partly by the Immune deficiency (IMD) pathway, which only gets activated by a type of peptidoglycan lacking in several medically important Gram-positive bacterial species such as Staphylococcus. Thus, the intestinal host defense against such bacterial strains remains poorly known. Here, we have used Staphylococcus xylosus to develop a model of intestinal infections by Gram-positive bacteria. S. xylosus behaves as an opportunistic pathogen in a septic injury model, being able to kill only flies immunodeficient either for the Toll pathway or the cellular response. When ingested, it is controlled by IMD-independent host intestinal defenses, yet flies eventually die. Having excluded an overreaction of the immune response and the action of toxins, we find that flies actually succumb to starvation, likely as a result of a competition for sucrose between the bacteria and the flies. Fat stores of wild-type flies are severely reduced within a day, a period when sucrose is not yet exhausted in the feeding solution. Interestingly, the Toll pathway mutant MyD88 is more resistant to the ingestion of S. xylosus and to starvation than wild-type flies. MyD88 flies do not rapidly deplete their fat stores when starved, in contrast to wild-type flies. Thus, we have uncovered a novel function of MyD88 in the regulation of metabolism that appears to be independent of its known roles in immunity and development. Close doi:10.1016/j.imbio.2012.07.027 Close
2012
Journal Articles
42.	Ezekowitz, Alan R B; Dimarcq, Jean-Luc; Kafatos, Fotis; Levashina, Elena A; Ferrandon, Dominique; Hetru, Charles; Imler, Jean-Luc; Reichhart, Jean-Marc Lawrence's book review unfair to Hoffmann Journal Article Curr. Biol., 22 (12), pp. R482, 2012, ISSN: 1879-0445. Links \| BibTeX @article{ezekowitz_lawrences_2012, title = {Lawrence's book review unfair to Hoffmann}, author = {R. Alan B. Ezekowitz and Jean-Luc Dimarcq and Fotis Kafatos and Elena A. Levashina and Dominique Ferrandon and Charles Hetru and Jean-Luc Imler and Jean-Marc Reichhart}, doi = {10.1016/j.cub.2012.05.015}, issn = {1879-0445}, year = {2012}, date = {2012-06-01}, journal = {Curr. Biol.}, volume = {22}, number = {12}, pages = {R482}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close doi:10.1016/j.cub.2012.05.015 Close
41.	Niehus, Sebastian; Giammarinaro, Philippe; Liégeois, Samuel; Quintin, Jessica; Ferrandon, Dominique Fly culture collapse disorder: detection, prophylaxis and eradication of the microsporidian parasite Tubulinosema ratisbonensis infecting Drosophila melanogaster Journal Article Fly (Austin), 6 (3), pp. 193–204, 2012, ISSN: 1933-6942. Abstract \| Links \| BibTeX @article{niehus_fly_2012b, title = {Fly culture collapse disorder: detection, prophylaxis and eradication of the microsporidian parasite Tubulinosema ratisbonensis infecting Drosophila melanogaster}, author = { Sebastian Niehus and Philippe Giammarinaro and Samuel Liégeois and Jessica Quintin and Dominique Ferrandon}, doi = {10.4161/fly.20896}, issn = {1933-6942}, year = {2012}, date = {2012-01-01}, journal = {Fly (Austin)}, volume = {6}, number = {3}, pages = {193--204}, abstract = {Drosophila melanogaster is a robust model to investigate many biological problems. It is however prone to some infections, which may endanger fly stocks if left unchecked for. One such infection is caused by an obligate fungal intracellular parasite, Tubulinosema ratisbonensis, which can be found in laboratory stocks. Here, we identify and briefly characterize a T. ratisbonensis strain that was infesting our Drosophila cultures and that required intensive measures to contain and eradicate the infection. We describe the phenotypes of infested stocks. We also report PCR-based techniques that allow the detection of infested stocks with a high sensitivity. We have developed a high-throughput qPCR assay that allows the efficient parallel screening of a large number of potentially-infested stocks. We also have investigated several prophylactic measures to prevent the further contamination of stocks, namely UV-exposure, ethanol treatment, bleaching, and desiccation. Bleaching was found to kill all spores. Other treatments were less effective but were found to be sufficient to prevent further contamination of noninfested stocks. Two treatments were efficacious in curing infested stocks (1) bleaching of eggs and subsequent raising of the larvae in clean vials; (2) fumagillin treatment. These cures only work on stocks that have not become too weak to withstand the procedures.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Drosophila melanogaster is a robust model to investigate many biological problems. It is however prone to some infections, which may endanger fly stocks if left unchecked for. One such infection is caused by an obligate fungal intracellular parasite, Tubulinosema ratisbonensis, which can be found in laboratory stocks. Here, we identify and briefly characterize a T. ratisbonensis strain that was infesting our Drosophila cultures and that required intensive measures to contain and eradicate the infection. We describe the phenotypes of infested stocks. We also report PCR-based techniques that allow the detection of infested stocks with a high sensitivity. We have developed a high-throughput qPCR assay that allows the efficient parallel screening of a large number of potentially-infested stocks. We also have investigated several prophylactic measures to prevent the further contamination of stocks, namely UV-exposure, ethanol treatment, bleaching, and desiccation. Bleaching was found to kill all spores. Other treatments were less effective but were found to be sufficient to prevent further contamination of noninfested stocks. Two treatments were efficacious in curing infested stocks (1) bleaching of eggs and subsequent raising of the larvae in clean vials; (2) fumagillin treatment. These cures only work on stocks that have not become too weak to withstand the procedures. Close doi:10.4161/fly.20896 Close
40.	Meister, Marie; Ferrandon, Dominique Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche Journal Article EMBO Rep., 13 (1), pp. 3–4, 2012, ISSN: 1469-3178. Links \| BibTeX @article{meister_immune_2012, title = {Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche}, author = { Marie Meister and Dominique Ferrandon}, doi = {10.1038/embor.2011.238}, issn = {1469-3178}, year = {2012}, date = {2012-01-01}, journal = {EMBO Rep.}, volume = {13}, number = {1}, pages = {3--4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close doi:10.1038/embor.2011.238 Close
2011
Journal Articles
39.	Imler, Jean-Luc; Ferrandon, Dominique [Innate immunity crowned 2011 Nobel Prize winner] Journal Article Med Sci (Paris), 27 , pp. 1019–24, 2011, ISSN: 0767-0974 (Print) 0767-0974 (Linking). Links \| BibTeX @article{imler_[innate_2011b, title = {[Innate immunity crowned 2011 Nobel Prize winner]}, author = {Jean-Luc Imler and Dominique Ferrandon}, url = {http://dx.doi.org.gate1.inist.fr/10.1051/medsci/20112711020}, doi = {10.1051/medsci/20112711020}, issn = {0767-0974 (Print) 0767-0974 (Linking)}, year = {2011}, date = {2011-11-01}, journal = {Med Sci (Paris)}, volume = {27}, pages = {1019--24}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close http://dx.doi.org.gate1.inist.fr/10.1051/medsci/20112711020 doi:10.1051/medsci/20112711020 Close
38.	Limmer, Stefanie; Haller, Samantha; Drenkard, Eliana; Lee, Janice; Yu, Shen; Kocks, Christine; Ausubel, Frederick M; Ferrandon, Dominique Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model Journal Article Proc. Natl. Acad. Sci. U.S.A., 108 (42), pp. 17378–17383, 2011, ISSN: 1091-6490. Abstract \| Links \| BibTeX @article{limmer_pseudomonas_2011b, title = {Pseudomonas aeruginosa RhlR is required to neutralize the cellular immune response in a Drosophila melanogaster oral infection model}, author = { Stefanie Limmer and Samantha Haller and Eliana Drenkard and Janice Lee and Shen Yu and Christine Kocks and Frederick M. Ausubel and Dominique Ferrandon}, doi = {10.1073/pnas.1114907108}, issn = {1091-6490}, year = {2011}, date = {2011-10-01}, journal = {Proc. Natl. Acad. Sci. U.S.A.}, volume = {108}, number = {42}, pages = {17378--17383}, abstract = {An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close An in-depth mechanistic understanding of microbial infection necessitates a molecular dissection of host-pathogen relationships. Both Drosophila melanogaster and Pseudomonas aeruginosa have been intensively studied. Here, we analyze the infection of D. melanogaster by P. aeruginosa by using mutants in both host and pathogen. We show that orally ingested P. aeruginosa crosses the intestinal barrier and then proliferates in the hemolymph, thereby causing the infected flies to die of bacteremia. Host defenses against ingested P. aeruginosa included an immune deficiency (IMD) response in the intestinal epithelium, systemic Toll and IMD pathway responses, and a cellular immune response controlling bacteria in the hemocoel. Although the observed cellular and intestinal immune responses appeared to act throughout the course of the infection, there was a late onset of the systemic IMD and Toll responses. In this oral infection model, P. aeruginosa PA14 did not require its type III secretion system or other well-studied virulence factors such as the two-component response regulator GacA or the protease AprA for virulence. In contrast, the quorum-sensing transcription factor RhlR, but surprisingly not LasR, played a key role in counteracting the cellular immune response against PA14, possibly at an early stage when only a few bacteria are present in the hemocoel. These results illustrate the power of studying infection from the dual perspective of host and pathogen by revealing that RhlR plays a more complex role during pathogenesis than previously appreciated. Close doi:10.1073/pnas.1114907108 Close
37.	Limmer, Stefanie; Quintin, Jessica; Hetru, Charles; Ferrandon, Dominique Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions Journal Article Curr Drug Targets, 12 (7), pp. 978–999, 2011, ISSN: 1873-5592. Abstract \| BibTeX @article{limmer_virulence_2011b, title = {Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions}, author = { Stefanie Limmer and Jessica Quintin and Charles Hetru and Dominique Ferrandon}, issn = {1873-5592}, year = {2011}, date = {2011-06-01}, journal = {Curr Drug Targets}, volume = {12}, number = {7}, pages = {978--999}, abstract = {To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well-studied Gram-negative bacterium Pseudomonas aeruginosa and infections by fungi of medical interest. These examples provide an overview over the current knowledge on Drosophila-pathogen interactions and illustrate the approaches that can be used to study those interactions. We also discuss the usefulness and limits of Drosophila infection models for studying specific host-pathogen interactions and high-throughput drug screening. Close
36.	Aoun, Richard Bou; Hetru, Charles; Troxler, Laurent; Doucet, Daniel; Ferrandon, Dominique; Matt, Nicolas Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster Journal Article J Innate Immun, 3 (1), pp. 52–64, 2011, ISSN: 1662-8128. Abstract \| Links \| BibTeX @article{bou_aoun_analysis_2011, title = {Analysis of thioester-containing proteins during the innate immune response of Drosophila melanogaster}, author = { Richard Bou Aoun and Charles Hetru and Laurent Troxler and Daniel Doucet and Dominique Ferrandon and Nicolas Matt}, doi = {10.1159/000321554}, issn = {1662-8128}, year = {2011}, date = {2011-01-01}, journal = {J Innate Immun}, volume = {3}, number = {1}, pages = {52--64}, abstract = {Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Thioester-containing proteins (TEPs) are conserved proteins among insects that are thought to be involved in innate immunity. In Drosophila, the Tep family is composed of 6 genes named Tep1-Tep6. In this study, we investigated the phylogeny, expression pattern and roles of these genes in the host defense of Drosophila. Protostomian Tep genes are clustered in 3 distinct branches, 1 of which is specific to mosquitoes. Most D. melanogaster Tep genes are expressed in hemocytes, can be induced in the fat body, and are expressed in specific regions of the hypodermis. This expression pattern is consistent with a role in innate immunity. However, we find that TEP1, TEP2, and TEP4 are not strictly required in the body cavity to fight several bacterial and fungal infections. One possibility is that Drosophila TEPs act redundantly or that their absence can be compensated by other components of the immune response. TEPs may thus provide a subtle selective advantage during evolution. Alternatively, they may be required in host defense against specific as yet unidentified natural pathogens of Drosophila. Close doi:10.1159/000321554 Close
35.	Meister, Marie; Ferrandon, Dominique Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche Journal Article EMBO Rep, 13 , pp. 3–4, 2011, ISSN: 1469-3178 (Electronic) 1469-221X (Linking). Links \| BibTeX @article{meister_immune_2011, title = {Immune cell transdifferentiation: a complex crosstalk between circulating immune cells and the haematopoietic niche}, author = { Marie Meister and Dominique Ferrandon}, doi = {embor2011238 [pii] 10.1038/embor.2011.238}, issn = {1469-3178 (Electronic) 1469-221X (Linking)}, year = {2011}, date = {2011-01-01}, journal = {EMBO Rep}, volume = {13}, pages = {3--4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close doi:embor2011238 [pii] 10.1038/embor.2011.238 Close
34.	Lee, Kwang-Zin; Ferrandon, Dominique Negative regulation of immune responses on the fly Journal Article EMBO J., 30 (6), pp. 988–990, 2011, ISSN: 1460-2075. Links \| BibTeX @article{lee_negative_2011b, title = {Negative regulation of immune responses on the fly}, author = { Kwang-Zin Lee and Dominique Ferrandon}, doi = {10.1038/emboj.2011.47}, issn = {1460-2075}, year = {2011}, date = {2011-01-01}, journal = {EMBO J.}, volume = {30}, number = {6}, pages = {988--990}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close doi:10.1038/emboj.2011.47 Close
33.	Nehme, Nadine T; Quintin, Jessica; Cho, Ju Hyun; Lee, Janice; Lafarge, Marie-Céline; Kocks, Christine; Ferrandon, Dominique Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections Journal Article PLoS ONE, 6 (3), pp. e14743, 2011, ISSN: 1932-6203. Abstract \| Links \| BibTeX @article{nehme_relative_2011b, title = {Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections}, author = { Nadine T. Nehme and Jessica Quintin and Ju Hyun Cho and Janice Lee and Marie-Céline Lafarge and Christine Kocks and Dominique Ferrandon}, doi = {10.1371/journal.pone.0014743}, issn = {1932-6203}, year = {2011}, date = {2011-01-01}, journal = {PLoS ONE}, volume = {6}, number = {3}, pages = {e14743}, abstract = {BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. METHODOLOGY/PRINCIPAL FINDINGS: In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. CONCLUSIONS/SIGNIFICANCE: Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen. Close doi:10.1371/journal.pone.0014743 Close
2010
Journal Articles
32.	Matskevich, Alexey A; Quintin, Jessica; Ferrandon, Dominique The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function Journal Article Eur. J. Immunol., 40 (5), pp. 1244–1254, 2010, ISSN: 1521-4141. Abstract \| Links \| BibTeX @article{matskevich_drosophila_2010b, title = {The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll-pathway activation function}, author = { Alexey A. Matskevich and Jessica Quintin and Dominique Ferrandon}, doi = {10.1002/eji.200940164}, issn = {1521-4141}, year = {2010}, date = {2010-05-01}, journal = {Eur. J. Immunol.}, volume = {40}, number = {5}, pages = {1244--1254}, abstract = {The Drosophila Toll-signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the beta-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3(hades) mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll-independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The Drosophila Toll-signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the beta-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3(hades) mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll-independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms. Close doi:10.1002/eji.200940164 Close
31.	Pospisilik, Andrew J; Schramek, Daniel; Schnidar, Harald; Cronin, Shane J F; Nehme, Nadine T; Zhang, Xiaoyun; Knauf, Claude; Cani, Patrice D; Aumayr, Karin; Todoric, Jelena; Bayer, Martina; Haschemi, Arvand; Puviindran, Vijitha; Tar, Krisztina; Orthofer, Michael; Neely, Gregory G; Dietzl, Georg; Manoukian, Armen; Funovics, Martin; Prager, Gerhard; Wagner, Oswald; Ferrandon, Dominique; Aberger, Fritz; Hui, Chi-chung; Esterbauer, Harald; Penninger, Josef M Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate Journal Article Cell, 140 (1), pp. 148–160, 2010, ISSN: 1097-4172. Abstract \| Links \| BibTeX @article{pospisilik_drosophila_2010b, title = {Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate}, author = { J. Andrew Pospisilik and Daniel Schramek and Harald Schnidar and Shane J. F. Cronin and Nadine T. Nehme and Xiaoyun Zhang and Claude Knauf and Patrice D. Cani and Karin Aumayr and Jelena Todoric and Martina Bayer and Arvand Haschemi and Vijitha Puviindran and Krisztina Tar and Michael Orthofer and G. Gregory Neely and Georg Dietzl and Armen Manoukian and Martin Funovics and Gerhard Prager and Oswald Wagner and Dominique Ferrandon and Fritz Aberger and Chi-chung Hui and Harald Esterbauer and Josef M. Penninger}, doi = {10.1016/j.cell.2009.12.027}, issn = {1097-4172}, year = {2010}, date = {2010-01-01}, journal = {Cell}, volume = {140}, number = {1}, pages = {148--160}, abstract = {Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Over 1 billion people are estimated to be overweight, placing them at risk for diabetes, cardiovascular disease, and cancer. We performed a systems-level genetic dissection of adiposity regulation using genome-wide RNAi screening in adult Drosophila. As a follow-up, the resulting approximately 500 candidate obesity genes were functionally classified using muscle-, oenocyte-, fat-body-, and neuronal-specific knockdown in vivo and revealed hedgehog signaling as the top-scoring fat-body-specific pathway. To extrapolate these findings into mammals, we generated fat-specific hedgehog-activation mutant mice. Intriguingly, these mice displayed near total loss of white, but not brown, fat compartments. Mechanistically, activation of hedgehog signaling irreversibly blocked differentiation of white adipocytes through direct, coordinate modulation of early adipogenic factors. These findings identify a role for hedgehog signaling in white/brown adipocyte determination and link in vivo RNAi-based scanning of the Drosophila genome to regulation of adipocyte cell fate in mammals. Close doi:10.1016/j.cell.2009.12.027 Close
2009
Journal Articles
30.	Mishima, Yumiko; Quintin, Jessica; Aimanianda, Vishukumar; Kellenberger, Christine; Coste, Franck; Clavaud, Cecile; Hetru, Charles; Hoffmann, Jules A; Latgé, Jean-Paul; Ferrandon, Dominique; Roussel, Alain The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors Journal Article J. Biol. Chem., 284 (42), pp. 28687–28697, 2009, ISSN: 1083-351X. Abstract \| Links \| BibTeX @article{mishima_n-terminal_2009, title = {The N-terminal domain of Drosophila Gram-negative binding protein 3 (GNBP3) defines a novel family of fungal pattern recognition receptors}, author = { Yumiko Mishima and Jessica Quintin and Vishukumar Aimanianda and Christine Kellenberger and Franck Coste and Cecile Clavaud and Charles Hetru and Jules A. Hoffmann and Jean-Paul Latgé and Dominique Ferrandon and Alain Roussel}, doi = {10.1074/jbc.M109.034587}, issn = {1083-351X}, year = {2009}, date = {2009-10-01}, journal = {J. Biol. Chem.}, volume = {284}, number = {42}, pages = {28687--28697}, abstract = {Gram-negative binding protein 3 (GNBP3), a pattern recognition receptor that circulates in the hemolymph of Drosophila, is responsible for sensing fungal infection and triggering Toll pathway activation. Here, we report that GNBP3 N-terminal domain binds to fungi upon identifying long chains of beta-1,3-glucans in the fungal cell wall as a major ligand. Interestingly, this domain fails to interact strongly with short oligosaccharides. The crystal structure of GNBP3-Nter reveals an immunoglobulin-like fold in which the glucan binding site is masked by a loop that is highly conserved among glucan-binding proteins identified in several insect orders. Structure-based mutagenesis experiments reveal an essential role for this occluding loop in discriminating between short and long polysaccharides. The displacement of the occluding loop is necessary for binding and could explain the specificity of the interaction with long chain structured polysaccharides. This represents a novel mechanism for beta-glucan recognition.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Gram-negative binding protein 3 (GNBP3), a pattern recognition receptor that circulates in the hemolymph of Drosophila, is responsible for sensing fungal infection and triggering Toll pathway activation. Here, we report that GNBP3 N-terminal domain binds to fungi upon identifying long chains of beta-1,3-glucans in the fungal cell wall as a major ligand. Interestingly, this domain fails to interact strongly with short oligosaccharides. The crystal structure of GNBP3-Nter reveals an immunoglobulin-like fold in which the glucan binding site is masked by a loop that is highly conserved among glucan-binding proteins identified in several insect orders. Structure-based mutagenesis experiments reveal an essential role for this occluding loop in discriminating between short and long polysaccharides. The displacement of the occluding loop is necessary for binding and could explain the specificity of the interaction with long chain structured polysaccharides. This represents a novel mechanism for beta-glucan recognition. Close doi:10.1074/jbc.M109.034587 Close
29.	Ferrandon, Dominique Host tolerance versus resistance and microbial virulence in the host-pathogen equation Journal Article Cell Host Microbe, 6 (3), pp. 203–205, 2009, ISSN: 1934-6069. Abstract \| Links \| BibTeX @article{ferrandon_host_2009b, title = {Host tolerance versus resistance and microbial virulence in the host-pathogen equation}, author = { Dominique Ferrandon}, doi = {10.1016/j.chom.2009.08.010}, issn = {1934-6069}, year = {2009}, date = {2009-09-01}, journal = {Cell Host Microbe}, volume = {6}, number = {3}, pages = {203--205}, abstract = {To deal with an infection, the organism resorts to nonmutually exclusive strategies: resistance, that is, neutralization or destruction of the pathogen; or tolerance, the ability to withstand damages inflicted by the pathogen or by host defense. In this issue of Cell Host & Microbe, Shinzawa et al. (2009) identify p38-mediated phagocytic encapsulation as a potential tolerance mechanism.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close To deal with an infection, the organism resorts to nonmutually exclusive strategies: resistance, that is, neutralization or destruction of the pathogen; or tolerance, the ability to withstand damages inflicted by the pathogen or by host defense. In this issue of Cell Host & Microbe, Shinzawa et al. (2009) identify p38-mediated phagocytic encapsulation as a potential tolerance mechanism. Close doi:10.1016/j.chom.2009.08.010 Close
28.	Cronin, Shane J F; Nehme, Nadine T; Limmer, Stefanie; Liegeois, Samuel; Pospisilik, Andrew J; Schramek, Daniel; Leibbrandt, Andreas; de Simoes, Ricardo Matos; Gruber, Susanne; Puc, Urszula; Ebersberger, Ingo; Zoranovic, Tamara; Neely, Gregory G; von Haeseler, Arndt; Ferrandon, Dominique; Penninger, Josef M Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection Journal Article Science, 325 (5938), pp. 340–343, 2009, ISSN: 1095-9203. Abstract \| Links \| BibTeX @article{cronin_genome-wide_2009b, title = {Genome-wide RNAi screen identifies genes involved in intestinal pathogenic bacterial infection}, author = { Shane J. F. Cronin and Nadine T. Nehme and Stefanie Limmer and Samuel Liegeois and J. Andrew Pospisilik and Daniel Schramek and Andreas Leibbrandt and Ricardo de Matos Simoes and Susanne Gruber and Urszula Puc and Ingo Ebersberger and Tamara Zoranovic and G. Gregory Neely and Arndt von Haeseler and Dominique Ferrandon and Josef M. Penninger}, doi = {10.1126/science.1173164}, issn = {1095-9203}, year = {2009}, date = {2009-01-01}, journal = {Science}, volume = {325}, number = {5938}, pages = {340--343}, abstract = {Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Innate immunity represents the first line of defense in animals. We report a genome-wide in vivo Drosophila RNA interference screen to uncover genes involved in susceptibility or resistance to intestinal infection with the bacterium Serratia marcescens. We first employed whole-organism gene suppression, followed by tissue-specific silencing in gut epithelium or hemocytes to identify several hundred genes involved in intestinal antibacterial immunity. Among the pathways identified, we showed that the JAK-STAT signaling pathway controls host defense in the gut by regulating stem cell proliferation and thus epithelial cell homeostasis. Therefore, we revealed multiple genes involved in antibacterial defense and the regulation of innate immunity. Close doi:10.1126/science.1173164 Close
2008
Journal Articles
27.	Roetzer, Andreas; Gregori, Christa; Jennings, Ann Marie; Quintin, Jessica; Ferrandon, Dominique; Butler, Geraldine; Kuchler, Karl; Ammerer, Gustav; Schüller, Christoph Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors Journal Article Mol. Microbiol., 69 (3), pp. 603–620, 2008, ISSN: 1365-2958. Abstract \| Links \| BibTeX @article{roetzer_candida_2008b, title = {Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors}, author = { Andreas Roetzer and Christa Gregori and Ann Marie Jennings and Jessica Quintin and Dominique Ferrandon and Geraldine Butler and Karl Kuchler and Gustav Ammerer and Christoph Schüller}, doi = {10.1111/j.1365-2958.2008.06301.x}, issn = {1365-2958}, year = {2008}, date = {2008-01-01}, journal = {Mol. Microbiol.}, volume = {69}, number = {3}, pages = {603--620}, abstract = {We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close We determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata. Close doi:10.1111/j.1365-2958.2008.06301.x Close
2007
Journal Articles
26.	Ferrandon, Dominique; Imler, Jean-Luc; Hetru, Charles; Hoffmann, Jules A The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections Journal Article Nat Rev Immunol, 7 , pp. 862–74, 2007. Abstract \| BibTeX @article{ferrandon_drosophila_2007b, title = {The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections}, author = {Dominique Ferrandon and Jean-Luc Imler and Charles Hetru and Jules A. Hoffmann}, year = {2007}, date = {2007-11-01}, journal = {Nat Rev Immunol}, volume = {7}, pages = {862--74}, abstract = {A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close A hallmark of the potent, multifaceted antimicrobial defence of Drosophila melanogaster is the challenge-induced synthesis of several families of antimicrobial peptides by cells in the fat body. The basic mechanisms of recognition of various types of microbial infections by the adult fly are now understood, often in great detail. We have further gained valuable insight into the infection-induced gene reprogramming by nuclear factor-kappaB (NF-kappaB) family members under the dependence of complex intracellular signalling cascades. The striking parallels between the adult fly response and mammalian innate immune defences described below point to a common ancestry and validate the relevance of the fly defence as a paradigm for innate immunity. Close
25.	Ferrandon, Dominique Ubiquitin-proteasome: pallbearer carries the deceased to the grave Journal Article Immunity, 27 (4), pp. 541–544, 2007, ISSN: 1074-7613. Abstract \| Links \| BibTeX @article{ferrandon_ubiquitin-proteasome:_2007b, title = {Ubiquitin-proteasome: pallbearer carries the deceased to the grave}, author = { Dominique Ferrandon}, doi = {10.1016/j.immuni.2007.10.003}, issn = {1074-7613}, year = {2007}, date = {2007-10-01}, journal = {Immunity}, volume = {27}, number = {4}, pages = {541--544}, abstract = {Phagocytosis is a complex process that involves multiple cellular functions. In this issue of Immunity, Silva et al. (2007) report that a protein ubiquitylation complex and the proteasome are required for the clearance of apoptotic cells in Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Phagocytosis is a complex process that involves multiple cellular functions. In this issue of Immunity, Silva et al. (2007) report that a protein ubiquitylation complex and the proteasome are required for the clearance of apoptotic cells in Drosophila. Close doi:10.1016/j.immuni.2007.10.003 Close
24.	Ferrandon, Dominique; Gottar, Marie; Gobert, Vanessa [New mechanism for detection of infections using the innate immune system of animals] Journal Article Med Sci (Paris), 23 (8-9), pp. 707–709, 2007, ISSN: 0767-0974. Links \| BibTeX @article{ferrandon_[new_2007b, title = {[New mechanism for detection of infections using the innate immune system of animals]}, author = { Dominique Ferrandon and Marie Gottar and Vanessa Gobert}, doi = {10.1051/medsci/20072389707}, issn = {0767-0974}, year = {2007}, date = {2007-09-01}, journal = {Med Sci (Paris)}, volume = {23}, number = {8-9}, pages = {707--709}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close doi:10.1051/medsci/20072389707 Close
23.	Nehme, Nadine T; Liégeois, Samuel; Kele, Beatrix; Giammarinaro, Philippe; Pradel, Elizabeth; Hoffmann, Jules A; Ewbank, Jonathan J; Ferrandon, Dominique A model of bacterial intestinal infections in Drosophila melanogaster Journal Article PLoS Pathog., 3 (11), pp. e173, 2007, ISSN: 1553-7374. Abstract \| Links \| BibTeX @article{nehme_model_2007b, title = {A model of bacterial intestinal infections in Drosophila melanogaster}, author = { Nadine T. Nehme and Samuel Liégeois and Beatrix Kele and Philippe Giammarinaro and Elizabeth Pradel and Jules A. Hoffmann and Jonathan J. Ewbank and Dominique Ferrandon}, doi = {10.1371/journal.ppat.0030173}, issn = {1553-7374}, year = {2007}, date = {2007-01-01}, journal = {PLoS Pathog.}, volume = {3}, number = {11}, pages = {e173}, abstract = {Serratia marcescens is an entomopathogenic bacterium that opportunistically infects a wide range of hosts, including humans. In a model of septic injury, if directly introduced into the body cavity of Drosophila, this pathogen is insensitive to the host's systemic immune response and kills flies in a day. We find that S. marcescens resistance to the Drosophila immune deficiency (imd)-mediated humoral response requires the bacterial lipopolysaccharide O-antigen. If ingested by Drosophila, bacteria cross the gut and penetrate the body cavity. During this passage, the bacteria can be observed within the cells of the intestinal epithelium. In such an oral infection model, the flies succumb to infection only after 6 days. We demonstrate that two complementary host defense mechanisms act together against such food-borne infection: an antimicrobial response in the intestine that is regulated by the imd pathway and phagocytosis by hemocytes of bacteria that have escaped into the hemolymph. Interestingly, bacteria present in the hemolymph elicit a systemic immune response only when phagocytosis is blocked. Our observations support a model wherein peptidoglycan fragments released during bacterial growth activate the imd pathway and do not back a proposed role for phagocytosis in the immune activation of the fat body. Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Serratia marcescens is an entomopathogenic bacterium that opportunistically infects a wide range of hosts, including humans. In a model of septic injury, if directly introduced into the body cavity of Drosophila, this pathogen is insensitive to the host's systemic immune response and kills flies in a day. We find that S. marcescens resistance to the Drosophila immune deficiency (imd)-mediated humoral response requires the bacterial lipopolysaccharide O-antigen. If ingested by Drosophila, bacteria cross the gut and penetrate the body cavity. During this passage, the bacteria can be observed within the cells of the intestinal epithelium. In such an oral infection model, the flies succumb to infection only after 6 days. We demonstrate that two complementary host defense mechanisms act together against such food-borne infection: an antimicrobial response in the intestine that is regulated by the imd pathway and phagocytosis by hemocytes of bacteria that have escaped into the hemolymph. Interestingly, bacteria present in the hemolymph elicit a systemic immune response only when phagocytosis is blocked. Our observations support a model wherein peptidoglycan fragments released during bacterial growth activate the imd pathway and do not back a proposed role for phagocytosis in the immune activation of the fat body. Thanks to the genetic tools available in both host and pathogen, the molecular dissection of the interactions between S. marcescens and Drosophila will provide a useful paradigm for deciphering intestinal pathogenesis. Close doi:10.1371/journal.ppat.0030173 Close
2006
Journal Articles
22.	Gottar, Marie; Gobert, Vanessa ; Matskevich, Alexey A; Reichhart, Jean-Marc ; Wang, Chengshu ; Butt, Tariq M; Belvin, Marcia ; Hoffmann, Jules A; Ferrandon, Dominique Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors Journal Article Cell, 127 (7), pp. 1425–1437, 2006, ISSN: 0092-8674. Abstract \| Links \| BibTeX @article{gottar_dual_2006, title = {Dual detection of fungal infections in Drosophila via recognition of glucans and sensing of virulence factors}, author = { Marie Gottar and Vanessa Gobert and Alexey A. Matskevich and Jean-Marc Reichhart and Chengshu Wang and Tariq M. Butt and Marcia Belvin and Jules A. Hoffmann and Dominique Ferrandon}, doi = {10.1016/j.cell.2006.10.046}, issn = {0092-8674}, year = {2006}, date = {2006-12-01}, journal = {Cell}, volume = {127}, number = {7}, pages = {1425--1437}, abstract = {The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The Drosophila immune system discriminates between various types of infections and activates appropriate signal transduction pathways to combat the invading microorganisms. The Toll pathway is required for the host response against fungal and most Gram-positive bacterial infections. The sensing of Gram-positive bacteria is mediated by the pattern recognition receptors PGRP-SA and GNBP1 that cooperate to detect the presence of infections in the host. Here, we report that GNBP3 is a pattern recognition receptor that is required for the detection of fungal cell wall components. Strikingly, we find that there is a second, parallel pathway acting jointly with GNBP3. The Drosophila Persephone protease activates the Toll pathway when proteolytically matured by the secreted fungal virulence factor PR1. Thus, the detection of fungal infections in Drosophila relies both on the recognition of invariant microbial patterns and on monitoring the effects of virulence factors on the host. Close doi:10.1016/j.cell.2006.10.046 Close
2005
Journal Articles
21.	Kocks, Christine; Cho, Ju Hyun ; Nehme, Nadine ; Ulvila, Johanna ; Pearson, Alan M; Meister, Marie ; Strom, Charles ; Conto, Stephanie L; Hetru, Charles ; Stuart, Lynda M; Stehle, Thilo ; Hoffmann, Jules A; Reichhart, Jean-Marc ; Ferrandon, Dominique ; Rämet, Mika ; Ezekowitz, Alan R B Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila Journal Article Cell, 123 (2), pp. 335–346, 2005, ISSN: 0092-8674. Abstract \| Links \| BibTeX @article{kocks_eater_2005, title = {Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila}, author = { Christine Kocks and Ju Hyun Cho and Nadine Nehme and Johanna Ulvila and Alan M. Pearson and Marie Meister and Charles Strom and Stephanie L. Conto and Charles Hetru and Lynda M. Stuart and Thilo Stehle and Jules A. Hoffmann and Jean-Marc Reichhart and Dominique Ferrandon and Mika Rämet and R. Alan B. Ezekowitz}, doi = {10.1016/j.cell.2005.08.034}, issn = {0092-8674}, year = {2005}, date = {2005-10-01}, journal = {Cell}, volume = {123}, number = {2}, pages = {335--346}, abstract = {Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Flies lacking the eater gene displayed normal responses in NF-kappaB-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo. Close doi:10.1016/j.cell.2005.08.034 Close
2004
Journal Articles
20.	Imler, Jean-Luc; Ferrandon, Dominique ; Royet, Julien ; Reichhart, Jean-Marc ; Hetru, Charles ; Hoffmann, Jules A Toll-dependent and Toll-independent immune responses in Drosophila Journal Article Journal of Endotoxin Research, 10 (4), pp. 241–246, 2004, ISSN: 0968-0519. Abstract \| Links \| BibTeX @article{imler_toll-dependent_2004, title = {Toll-dependent and Toll-independent immune responses in Drosophila}, author = { Jean-Luc Imler and Dominique Ferrandon and Julien Royet and Jean-Marc Reichhart and Charles Hetru and Jules A. Hoffmann}, doi = {10.1179/096805104225005887}, issn = {0968-0519}, year = {2004}, date = {2004-01-01}, journal = {Journal of Endotoxin Research}, volume = {10}, number = {4}, pages = {241--246}, abstract = {The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs. Close doi:10.1179/096805104225005887 Close
19.	Ferrandon, Dominique; Imler, Jean-Luc; Hoffmann, Jules A Sensing infection in Drosophila: Toll and beyond Journal Article Semin Immunol, 16 , pp. 43–53, 2004, ISSN: 1044-5323. Abstract \| BibTeX @article{ferrandon_sensing_2004b, title = {Sensing infection in Drosophila: Toll and beyond}, author = {Dominique Ferrandon and Jean-Luc Imler and Jules A. Hoffmann}, issn = {1044-5323}, year = {2004}, date = {2004-01-01}, journal = {Semin Immunol}, volume = {16}, pages = {43--53}, abstract = {Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs).}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close Drosophila has evolved a potent immune system that is somewhat adapted to the nature of infections through the selective activation of either one of two NF-kappa B-like signalling pathways, the Toll and IMD (Immune deficiency) pathways. In contrast to the mammalian system, the Toll receptor does not act as a pattern recognition receptor (PRR) but as a cytokine receptor. The sensing of microbial infections is achieved by at least four PRRs that belong to two distinct families: the peptidoglycan recognition proteins (PGRPs) and the Gram-negative binding proteins (GNBPs)/beta-glucan recognition proteins (beta GRPs). Close
18.	Ferrandon, Dominique; Royet, Julien La réponse immunitaire chez la Drosophile Journal Article Regards sur la biochimie, 1 , pp. 27–33, 2004. BibTeX @article{ferrandon_reponse_2004b, title = {La réponse immunitaire chez la Drosophile}, author = { Dominique Ferrandon and Julien Royet}, year = {2004}, date = {2004-01-01}, journal = {Regards sur la biochimie}, volume = {1}, pages = {27--33}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close
2003
Journal Articles
17.	Gobert, Vanessa; Gottar, Marie; Matskevich, Alexey A; Rutschmann, Sophie; Royet, Julien; Belvin, Marcia; Hoffmann, Jules A; Ferrandon, Dominique Dual activation of the Drosophila toll pathway by two pattern recognition receptors Journal Article Science, 302 (5653), pp. 2126–2130, 2003, ISSN: 1095-9203. Abstract \| Links \| BibTeX @article{gobert_dual_2003, title = {Dual activation of the Drosophila toll pathway by two pattern recognition receptors}, author = { Vanessa Gobert and Marie Gottar and Alexey A. Matskevich and Sophie Rutschmann and Julien Royet and Marcia Belvin and Jules A. Hoffmann and Dominique Ferrandon}, doi = {10.1126/science.1085432}, issn = {1095-9203}, year = {2003}, date = {2003-12-01}, journal = {Science}, volume = {302}, number = {5653}, pages = {2126--2130}, abstract = {The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects. Close doi:10.1126/science.1085432 Close
16.	Kurz, Léopold C; Chauvet, Sophie; Andrès, Emmanuel; Aurouze, Marianne; Vallet, Isabelle; Michel, Gérard P F; Uh, Mitch; Celli, Jean; Filloux, Alain; Bentzmann, Sophie De; Steinmetz, Ivo; Hoffmann, Jules A; Finlay, Brett B; Gorvel, Jean-Pierre; Ferrandon, Dominique; Ewbank, Jonathan J Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening Journal Article Embo J, 22 , pp. 1451–60, 2003, ISBN: 0261-4189. Abstract \| Links \| BibTeX @article{kurz_virulence_2003b, title = {Virulence factors of the human opportunistic pathogen Serratia marcescens identified by in vivo screening}, author = {C. Léopold Kurz and Sophie Chauvet and Emmanuel Andrès and Marianne Aurouze and Isabelle Vallet and Gérard P. F. Michel and Mitch Uh and Jean Celli and Alain Filloux and Sophie De Bentzmann and Ivo Steinmetz and Jules A. Hoffmann and B. Brett Finlay and Jean-Pierre Gorvel and Dominique Ferrandon and Jonathan J. Ewbank}, doi = {10.1093/emboj/cdg159}, isbn = {0261-4189}, year = {2003}, date = {2003-04-01}, journal = {Embo J}, volume = {22}, pages = {1451--60}, abstract = {The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The human opportunistic pathogen Serratia marcescens is a bacterium with a broad host range, and represents a growing problem for public health. Serratia marcescens kills Caenorhabditis elegans after colonizing the nematode's intestine. We used C.elegans to screen a bank of transposon-induced S.marcescens mutants and isolated 23 clones with an attenuated virulence. Nine of the selected bacterial clones also showed a reduced virulence in an insect model of infection. Of these, three exhibited a reduced cytotoxicity in vitro, and among them one was also markedly attenuated in its virulence in a murine lung infection model. For 21 of the 23 mutants, the transposon insertion site was identified. This revealed that among the genes necessary for full in vivo virulence are those that function in lipopolysaccharide (LPS) biosynthesis, iron uptake and hemolysin production. Using this system we also identified novel conserved virulence factors required for Pseudomonas aeruginosa pathogenicity. This study extends the utility of C.elegans as an in vivo model for the study of bacterial virulence and advances the molecular understanding of S.marcescens pathogenicity. Close doi:10.1093/emboj/cdg159 Close
2002
Journal Articles
15.	Gottar, Marie; Gobert, Vanessa; Michel, Tatiana; Belvin, Marcia; Duyk, Geoffrey; Hoffmann, Jules A; Ferrandon, Dominique; Royet, Julien The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein Journal Article Nature, 416 , pp. 640–644, 2002, ISBN: 0028-0836. Abstract \| Links \| BibTeX @article{gottar_drosophila_2002b, title = {The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein}, author = {Marie Gottar and Vanessa Gobert and Tatiana Michel and Marcia Belvin and Geoffrey Duyk and Jules A. Hoffmann and Dominique Ferrandon and Julien Royet}, doi = {10.1038/nature734}, isbn = {0028-0836}, year = {2002}, date = {2002-03-01}, journal = {Nature}, volume = {416}, pages = {640--644}, abstract = {The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. Close doi:10.1038/nature734 Close
14.	Ferrandon, Dominique; Royet, Julien La drosophile : un modèle pour l'étude de la réponse immunitaire des invertébrés Journal Article Regards sur la biochimie, 1 , pp. 27–33, 2002. BibTeX @article{ferrandon_drosophile_2002, title = {La drosophile : un modèle pour l'étude de la réponse immunitaire des invertébrés}, author = { Dominique Ferrandon and Julien Royet}, year = {2002}, date = {2002-01-01}, journal = {Regards sur la biochimie}, volume = {1}, pages = {27--33}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close
13.	Rutschmann, Sophie; Kilinc, A; Ferrandon, Dominique The Toll pathway is required for resistance to Gram-positive bacterial infections in Drosophila. Journal Article J Immunol, 168 , pp. 1542–1546, 2002. BibTeX @article{rutschmann_toll_2002b, title = {The Toll pathway is required for resistance to Gram-positive bacterial infections in Drosophila.}, author = { Sophie Rutschmann and A. Kilinc and Dominique Ferrandon}, year = {2002}, date = {2002-01-01}, journal = {J Immunol}, volume = {168}, pages = {1542--1546}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close
Incollections
12.	Royet, Julien; Meister, Marie; Ferrandon, Dominique Humoral and cellular responses in textitDrosophila innate immunity Incollection Ezekowitz, R A B; Hoffmann, J A (Ed.): Innate Immunity, The Humana Press Inc., Totowa, 2002. BibTeX @incollection{royet_humoral_2002, title = {Humoral and cellular responses in textitDrosophila innate immunity}, author = { Julien Royet and Marie Meister and Dominique Ferrandon}, editor = {Ezekowitz, R. A. B. and Hoffmann, J. A.}, year = {2002}, date = {2002-01-01}, booktitle = {Innate Immunity}, publisher = {The Humana Press Inc.}, address = {Totowa}, keywords = {}, pubstate = {published}, tppubtype = {incollection} } Close
2001
Journal Articles
11.	Georgel, Philippe; Naitza, S; Kappler, Christine ; Ferrandon, Dominique ; Zachary, Daniel ; Swimmer, C; Kopczynski, C; Duyk, G; Reichhart, Jean-Marc ; Hoffmann, Jules A Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis Journal Article Dev. Cell, 1 (4), pp. 503–514, 2001, ISSN: 1534-5807. Abstract \| BibTeX @article{georgel_drosophila_2001, title = {Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis}, author = { Philippe Georgel and S. Naitza and Christine Kappler and Dominique Ferrandon and Daniel Zachary and C. Swimmer and C. Kopczynski and G. Duyk and Jean-Marc Reichhart and Jules A. Hoffmann}, issn = {1534-5807}, year = {2001}, date = {2001-10-01}, journal = {Dev. Cell}, volume = {1}, number = {4}, pages = {503--514}, abstract = {We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close We report the molecular characterization of the immune deficiency (imd) gene, which controls antibacterial defense in Drosophila. imd encodes a protein with a death domain similar to that of mammalian RIP (receptor interacting protein), a protein that plays a role in both NF-kappaB activation and apoptosis. We show that imd functions upstream of the DmIKK signalosome and the caspase DREDD in the control of antibacterial peptide genes. Strikingly, overexpression of imd leads to constitutive transcription of these genes and to apoptosis, and both effects are blocked by coexpression of the caspase inhibitor P35. We also show that imd is involved in the apoptotic response to UV irradiation. These data raise the possibility that antibacterial response and apoptosis share common control elements in Drosophila. Close
10.	Jung, Alain C; Criqui, M C; Rutschmann, Sophie; Hoffmann, Jules A; Ferrandon, Dominique A microfluorometer assay to measure the expression of beta-galactosidase and green fluorescent protein reporter genes in single Drosophila flies Journal Article BioTechniques, 30 (3), pp. 594–598, 600–601, 2001, ISSN: 0736-6205. Abstract \| BibTeX @article{jung_microfluorometer_2001, title = {A microfluorometer assay to measure the expression of beta-galactosidase and green fluorescent protein reporter genes in single Drosophila flies}, author = {Alain C. Jung and M. C. Criqui and Sophie Rutschmann and Jules A. Hoffmann and Dominique Ferrandon}, issn = {0736-6205}, year = {2001}, date = {2001-03-01}, journal = {BioTechniques}, volume = {30}, number = {3}, pages = {594--598, 600--601}, abstract = {beta-galactosidase and green fluorescent protein (GFP) are among the most commonly used reporter genes to monitor gene expression in various organisms including Drosophila melanogaster. Their expression is usually detected in a qualitative way by direct microscopic observations of cells, tissues, or whole animals. To measure in vivo the inducibility of two antimicrobial peptide genes expressed during the Drosophila innate immune response, we have adapted two reporter gene systems based on the beta-galactosidase enzymatic activity and GFP. We have designed a 96-well microplate fluorometric assay sensitive enough to quantify the expression of both reporter genes in single flies. The assay has enabled us to process efficiently and rapidly a large number of individual mutant flies generated during an ethylmethane sulfonate saturation mutagenesis of the Drosophila genome. This method may be used in any screen that requires the quantification of reporter gene activity in individual insects.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close beta-galactosidase and green fluorescent protein (GFP) are among the most commonly used reporter genes to monitor gene expression in various organisms including Drosophila melanogaster. Their expression is usually detected in a qualitative way by direct microscopic observations of cells, tissues, or whole animals. To measure in vivo the inducibility of two antimicrobial peptide genes expressed during the Drosophila innate immune response, we have adapted two reporter gene systems based on the beta-galactosidase enzymatic activity and GFP. We have designed a 96-well microplate fluorometric assay sensitive enough to quantify the expression of both reporter genes in single flies. The assay has enabled us to process efficiently and rapidly a large number of individual mutant flies generated during an ethylmethane sulfonate saturation mutagenesis of the Drosophila genome. This method may be used in any screen that requires the quantification of reporter gene activity in individual insects. Close
2000
Journal Articles
9.	Rutschmann, Sophie; Jung, Alain C; Zhou, R; Silverman, N; Hoffmann, Jules A; Ferrandon, Dominique Role of Drosophila IKK gamma in a toll-independent antibacterial immune response Journal Article Nat. Immunol., 1 (4), pp. 342–347, 2000, ISSN: 1529-2908. Abstract \| Links \| BibTeX @article{rutschmann_role_2000, title = {Role of Drosophila IKK gamma in a toll-independent antibacterial immune response}, author = {Sophie Rutschmann and Alain C. Jung and R. Zhou and N. Silverman and Jules A. Hoffmann and Dominique Ferrandon}, doi = {10.1038/79801}, issn = {1529-2908}, year = {2000}, date = {2000-10-01}, journal = {Nat. Immunol.}, volume = {1}, number = {4}, pages = {342--347}, abstract = {We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila. Close doi:10.1038/79801 Close
8.	Rutschmann, Sophie; Jung, Alain C; Hetru, Charles; Reichhart, Jean-Marc; Hoffmann, Jules A; Ferrandon, Dominique The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila Journal Article Immunity, 12 (5), pp. 569–580, 2000, ISSN: 1074-7613. Abstract \| BibTeX @article{rutschmann_rel_2000, title = {The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila}, author = {Sophie Rutschmann and Alain C. Jung and Charles Hetru and Jean-Marc Reichhart and Jules A. Hoffmann and Dominique Ferrandon}, issn = {1074-7613}, year = {2000}, date = {2000-05-01}, journal = {Immunity}, volume = {12}, number = {5}, pages = {569--580}, abstract = {We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close We have isolated two Drosophila lines that carry point mutations in the gene coding for the NF-KB-like factor DIF. Like mutants of the Toll pathway, Dif mutant flies are susceptible to fungal but not to bacterial infections. Genetic epistasis experiments demonstrate that Dif mediates the Toll-dependent control of the inducibility of the antifungal peptide gene Drosomycin. Strikingly, DIF alone is required for the antifungal response in adults, but is redundant in larvae with Dorsal, another Rel family member. In Drosophila, Dif appears to be dedicated to the antifungal defense elicited by fungi and gram-positive bacteria. We discuss in this light the possibility that NF-KB1/p50 might be required more specifically in the innate immune response against gram-positive bacteria in mammals. Close
7.	Ferrandon, Dominique; Hetru, Charles; Reichhart, Jean-Marc; Hoffmann, Jules A L'immunité innée : de la drosophile à l'homme Journal Article Pour la Science, Dossier Hors Série Octobre , pp. 8–12, 2000. BibTeX @article{ferrandon_immunite_2000, title = {L'immunité innée : de la drosophile à l'homme}, author = { Dominique Ferrandon and Charles Hetru and Jean-Marc Reichhart and Jules A. Hoffmann}, year = {2000}, date = {2000-01-01}, journal = {Pour la Science}, volume = {Dossier Hors Série Octobre}, pages = {8--12}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close
6.	Tzou, P; Ohresser, S; Ferrandon, Dominique; Capovilla, Maria; Reichhart, Jean-Marc; Lemaitre, Bruno; Hoffmann, Jules A; Imler, Jean-Luc Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia Journal Article Immunity, 13 , pp. 737–48., 2000, ISSN: 1074-7613. Abstract \| BibTeX @article{tzou_tissue-specific_2000b, title = {Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia}, author = {P. Tzou and S. Ohresser and Dominique Ferrandon and Maria Capovilla and Jean-Marc Reichhart and Bruno Lemaitre and Jules A. Hoffmann and Jean-Luc Imler}, issn = {1074-7613}, year = {2000}, date = {2000-01-01}, journal = {Immunity}, volume = {13}, pages = {737--48.}, abstract = {The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila. Close
1998
Journal Articles
5.	Ferrandon, Dominique; Jung, Alain C; Criqui, M; Lemaitre, Bruno; Uttenweiler-Joseph, S; Michaut, Lydia; Reichhart, Jean-Marc; Hoffmann, Jules A A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway Journal Article EMBO J., 17 (5), pp. 1217–1227, 1998, ISSN: 0261-4189. Abstract \| Links \| BibTeX @article{ferrandon_drosomycin-gfp_1998, title = {A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway}, author = { Dominique Ferrandon and Alain C. Jung and M. Criqui and Bruno Lemaitre and S. Uttenweiler-Joseph and Lydia Michaut and Jean-Marc Reichhart and Jules A. Hoffmann}, doi = {10.1093/emboj/17.5.1217}, issn = {0261-4189}, year = {1998}, date = {1998-08-01}, journal = {EMBO J.}, volume = {17}, number = {5}, pages = {1217--1227}, abstract = {A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury. One of these peptides, drosomycin, is active primarily against fungi. Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues. As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity. We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close A hallmark of the systemic antimicrobial response of Drosophila is the synthesis by the fat body of several antimicrobial peptides which are released into the hemolymph in response to a septic injury. One of these peptides, drosomycin, is active primarily against fungi. Using a drosomycin-green fluorescent protein (GFP) reporter gene, we now show that in addition to the fat body, a variety of epithelial tissues that are in direct contact with the external environment, including those of the respiratory, digestive and reproductive tracts, can express the antifungal peptide, suggesting a local response to infections affecting these barrier tissues. As is the case for vertebrate epithelia, insect epithelia appear to be more than passive physical barriers and are likely to constitute an active component of innate immunity. We also show that, in contrast to the systemic antifungal response, this local immune response is independent of the Toll pathway. Close doi:10.1093/emboj/17.5.1217 Close
4.	Reichhart, Jean-Marc; Ferrandon, Dominique Green Balancers. Journal Article D. I. S., 81 , pp. 201–202, 1998. Abstract \| BibTeX @article{reichhart_green_1998, title = {Green Balancers.}, author = { Jean-Marc Reichhart and Dominique Ferrandon}, year = {1998}, date = {1998-01-01}, journal = {D. I. S.}, volume = {81}, pages = {201--202}, abstract = {We have used the S65T green fluorescent protein (GFP ; (Chalfie et al., 1994) ; (Heim et al., 1995)) as a vital reporter to introduce a dominant innocuous marker onto the balancers of the three major chromosomes of D. melanogaster.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Close We have used the S65T green fluorescent protein (GFP ; (Chalfie et al., 1994) ; (Heim et al., 1995)) as a vital reporter to introduce a dominant innocuous marker onto the balancers of the three major chromosomes of D. melanogaster. Close

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