Publication
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. @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} } 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. |
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. @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} } |
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. @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} } 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. |
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. @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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). |
| 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. @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} } 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. |
| 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). @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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). |
| 43. | Ayyaz, Arshad; Giammarinaro, Philippe; Liégeois, Samuel; Lestradet, Matthieu; Ferrandon, Dominique Immunobiology, 218 (4), pp. 635–644, 2013, ISSN: 1878-3279. @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} } 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. |
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. @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} } |
| 41. | Niehus, Sebastian; Giammarinaro, Philippe; Liégeois, Samuel; Quintin, Jessica; Ferrandon, Dominique Fly (Austin), 6 (3), pp. 193–204, 2012, ISSN: 1933-6942. @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} } 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. |
| 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. @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} } |
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). @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} } |
| 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. @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} } 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. |
| 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. @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} } 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. |
| 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. @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} } 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. |
| 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). @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} } |
| 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. @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} } |
| 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. @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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. |
| 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. @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} } 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. |
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. @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} } 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. |
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. @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} } 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. |
| 25. | Ferrandon, Dominique Ubiquitin-proteasome: pallbearer carries the deceased to the grave Journal Article Immunity, 27 (4), pp. 541–544, 2007, ISSN: 1074-7613. @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} } 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. |
| 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. @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} } |
| 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. @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} } 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. |
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. @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} } 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. |
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. @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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). |
| 18. | Ferrandon, Dominique; Royet, Julien La réponse immunitaire chez la Drosophile Journal Article Regards sur la biochimie, 1 , pp. 27–33, 2004. @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} } |
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. @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} } 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. |
| 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. @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} } 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. |
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. @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} } 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. |
| 13. | 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. @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} } |
| 12. | 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. @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} } |
Incollections |
|
| 14. | 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. @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} } |
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. @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} } 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. |
| 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. @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} } 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. |
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. @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} } 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. |
| 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. @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} } 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. |
| 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. @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} } |
| 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. @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} } 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. |
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. @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} } 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. |
| 4. | Reichhart, Jean-Marc; Ferrandon, Dominique Green Balancers. Journal Article D. I. S., 81 , pp. 201–202, 1998. @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} } 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. |
Topics
Actuality and last Publications
- PhD proposal (from 2019)
- Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies
- Hyd ubiquitinates the NF-κB co-factor Akirin to activate an effective immune response in Drosophila
- Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization
- A mechanism for detecting microbial virulence in Drosophila
- Global Experts Recruitment Chinese Program
- Hyd ubiquitinates the NF-κB co-factor Akirin to activate an effective immune response in Drosophila
- Post-doctoral Position: Antiviral innate immunity in Drosophila
- Awards of medals of honor 2016 in the Alsace delegation of the CNRS
- Communication: Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack