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2014
Articles de journaux
16.	Haller, Samantha; Limmer, Stefanie; Ferrandon, Dominique Assessing Pseudomonas virulence with a nonmammalian host: Drosophila melanogaster Article de journal Methods Mol. Biol., 1149 , p. 723–740, 2014, ISSN: 1940-6029. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Antimicrobial Cationic Peptides, Biological Assay, Colony Count, Disease Models, Hemolymph, Host-Pathogen Interactions, Mammals, Microbial, Pseudomonas aeruginosa, Pseudomonas Infections, Reverse Transcriptase Polymerase Chain Reaction, Virulence @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 = {Animal, Antimicrobial Cationic Peptides, Biological Assay, Colony Count, Disease Models, Hemolymph, Host-Pathogen Interactions, Mammals, Microbial, Pseudomonas aeruginosa, Pseudomonas Infections, Reverse Transcriptase Polymerase Chain Reaction, Virulence}, pubstate = {published}, tppubtype = {article} } Fermer 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). Fermer doi:10.1007/978-1-4939-0473-0_56 Fermer
15.	Lestradet, Matthieu; Lee, Kwan Zin; Ferrandon, Dominique Drosophila as a model for intestinal infections Article de journal Methods Mol Biol, 1197 , p. 11–40, 2014, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking). Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Bacterial Physiological Phenomena, Disease Models, Gastrointestinal Tract, Host-Pathogen Interactions @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 = {Animal, Bacterial Physiological Phenomena, Disease Models, Gastrointestinal Tract, Host-Pathogen Interactions}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1007/978-1-4939-1261-2_2 Fermer
14.	Imler, Jean-Luc Overview of Drosophila immunity: a historical perspective Article de journal Developmental and Comparative Immunology, 42 (1), p. 3–15, 2014, ISSN: 1879-0089. Résumé \| Liens \| BibTeX \| Étiquettes: Allergy and Immunology, Animal, Antimicrobial Cationic Peptides, Antimicrobial peptides, History, Humans, IMD pathway, Immunity, Innate, innate immunity, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors @article{imler_overview_2014, title = {Overview of Drosophila immunity: a historical perspective}, author = { Jean-Luc Imler}, doi = {10.1016/j.dci.2013.08.018}, issn = {1879-0089}, year = {2014}, date = {2014-01-01}, journal = {Developmental and Comparative Immunology}, volume = {42}, number = {1}, pages = {3--15}, abstract = {The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field.}, keywords = {Allergy and Immunology, Animal, Antimicrobial Cationic Peptides, Antimicrobial peptides, History, Humans, IMD pathway, Immunity, Innate, innate immunity, Models, Pattern recognition receptors, Signal Transduction, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Fermer The functional analysis of genes from the model organism Drosophila melanogaster has provided invaluable information for many cellular and developmental or physiological processes, including immunity. The best-understood aspect of Drosophila immunity is the inducible humoral response, first recognized in 1972. This pioneering work led to a remarkable series of findings over the next 30 years, ranging from the identification and characterization of the antimicrobial peptides produced, to the deciphering of the signalling pathways activating the genes that encode them and, ultimately, to the discovery of the receptors sensing infection. These studies on an insect model coincided with a revival of the field of innate immunity, and had an unanticipated impact on the biomedical field. Fermer doi:10.1016/j.dci.2013.08.018 Fermer
2013
Articles de journaux
13.	Kobayashi, Taira; Ogawa, Michinaga; Sanada, Takahito; Mimuro, Hitomi; Kim, Minsoo; Ashida, Hiroshi; Akakura, Reiko; Yoshida, Mitsutaka; Kawalec, Magdalena; Reichhart, Jean-Marc; Mizushima, Tsunehiro; Sasakawa, Chihiro The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection Article de journal Cell Host Microbe, 13 (5), p. 570–583, 2013, ISSN: 1934-6069. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, Protein Binding, Protein Interaction Mapping, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors @article{kobayashi_shigella_2013, title = {The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection}, author = { Taira Kobayashi and Michinaga Ogawa and Takahito Sanada and Hitomi Mimuro and Minsoo Kim and Hiroshi Ashida and Reiko Akakura and Mitsutaka Yoshida and Magdalena Kawalec and Jean-Marc Reichhart and Tsunehiro Mizushima and Chihiro Sasakawa}, doi = {10.1016/j.chom.2013.04.012}, issn = {1934-6069}, year = {2013}, date = {2013-05-01}, journal = {Cell Host Microbe}, volume = {13}, number = {5}, pages = {570--583}, abstract = {Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection.}, keywords = {Animal, Bacillary, Bacterial, Bacterial Proteins, Caspases, Cell Death, Cell Line, Disease Models, DNA, Dysentery, Enzyme Inhibitors, Epithelial Cells, Escherichia coli, Gene Knockout Techniques, Guinea Pigs, Host-Pathogen Interactions, Humans, Initiator, Protein Binding, Protein Interaction Mapping, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors}, pubstate = {published}, tppubtype = {article} } Fermer Caspase-mediated inflammatory cell death acts as an intrinsic defense mechanism against infection. Bacterial pathogens deploy countermeasures against inflammatory cell death, but the mechanisms by which they do this remain largely unclear. In a screen for Shigella flexneri effectors that regulate cell death during infection, we discovered that Shigella infection induced acute inflammatory, caspase-4-dependent epithelial cell death, which is counteracted by the bacterial OspC3 effector. OspC3 interacts with the caspase-4-p19 subunit and inhibits its activation by preventing caspase-4-p19 and caspase-4-p10 heterodimerization by depositing the conserved OspC3 X1-Y-X₂-D-X₃ motif at the putative catalytic pocket of caspase-4. Infection of guinea pigs with a Shigella ospC3-deficient mutant resulted in enhanced inflammatory cell death and associated symptoms, correlating with decreased bacterial burdens. Salmonella Typhimurium and enteropathogenic Escherichia coli infection also induced caspase-4-dependent epithelial death. These findings highlight the importance of caspase-4-dependent innate immune responses and demonstrate that Shigella delivers a caspase-4-specific inhibitor to delay epithelial cell death and promote infection. Fermer doi:10.1016/j.chom.2013.04.012 Fermer
12.	Quintin, Jessica; Asmar, Joelle; Matskevich, Alexey A; Lafarge, Marie-Céline; Ferrandon, Dominique The Drosophila Toll pathway controls but does not clear Candida glabrata infections Article de journal J. Immunol., 190 (6), p. 2818–2827, 2013, ISSN: 1550-6606. Résumé \| Liens \| BibTeX \| Étiquettes: Adaptor Proteins, Animal, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, Immunologic, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence @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 = {Adaptor Proteins, Animal, Antigens, Candida glabrata, Candidiasis, Cells, Cultured, Differentiation, Disease Models, Immunologic, Phagocytosis, Receptors, Signal Transducing, Signal Transduction, Toll-Like Receptors, Virulence}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.4049/jimmunol.1201861 Fermer
11.	Ferrandon, Dominique The complementary facets of epithelial host defenses in the genetic model organism Drosophila melanogaster: from resistance to resilience Article de journal Curr. Opin. Immunol., 25 (1), p. 59–70, 2013, ISSN: 1879-0372. Résumé \| Liens \| BibTeX \| Étiquettes: Adult Stem Cells, Aging, Animal, Cell Proliferation, Disease Models, Enterocytes, Humans, Immunity, Intestinal Mucosa, Metagenome, Stem Cell Niche, Wound Healing @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 = {Adult Stem Cells, Aging, Animal, Cell Proliferation, Disease Models, Enterocytes, Humans, Immunity, Intestinal Mucosa, Metagenome, Stem Cell Niche, Wound Healing}, pubstate = {published}, tppubtype = {article} } Fermer 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). Fermer doi:10.1016/j.coi.2012.11.008 Fermer
10.	Ayyaz, Arshad; Giammarinaro, Philippe; Liégeois, Samuel; Lestradet, Matthieu; Ferrandon, Dominique A negative role for MyD88 in the resistance to starvation as revealed in an intestinal infection of Drosophila melanogaster with the Gram-positive bacterium Staphylococcus xylosus Article de journal Immunobiology, 218 (4), p. 635–644, 2013, ISSN: 1878-3279. Résumé \| Liens \| BibTeX \| Étiquettes: Adaptor Proteins, Animal, Antigens, Differentiation, Disease Models, Immunity, Immunologic, Innate, Intestinal Diseases, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors @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 = {Adaptor Proteins, Animal, Antigens, Differentiation, Disease Models, Immunity, Immunologic, Innate, Intestinal Diseases, Mucosal, Mutation, Receptors, Signal Transducing, Staphylococcal Infections, Staphylococcus, Starvation, Toll-Like Receptors}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1016/j.imbio.2012.07.027 Fermer
2011
Articles de journaux
9.	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 Article de journal Proc. Natl. Acad. Sci. U.S.A., 108 (42), p. 17378–17383, 2011, ISSN: 1091-6490. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Bacteremia, Bacterial Proteins, Cellular, Disease Models, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence @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 = {Animal, Bacteremia, Bacterial Proteins, Cellular, Disease Models, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1073/pnas.1114907108 Fermer
8.	Limmer, Stefanie; Quintin, Jessica; Hetru, Charles; Ferrandon, Dominique Virulence on the fly: Drosophila melanogaster as a model genetic organism to decipher host-pathogen interactions Article de journal Curr Drug Targets, 12 (7), p. 978–999, 2011, ISSN: 1873-5592. Résumé \| BibTeX \| Étiquettes: Animal, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, Microbial, Pseudomonas aeruginosa @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 = {Animal, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, Microbial, Pseudomonas aeruginosa}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer
2009
Articles de journaux
7.	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 Article de journal Science, 325 (5938), p. 340–343, 2009, ISSN: 1095-9203. Résumé \| Liens \| BibTeX \| Étiquettes: Genome, RNA Interference, Animal, Cell Proliferation, Drosophila melanogaster/genetics/immunology/microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/immunology/microbiology, Serratia marcescens, Serratia marcescens/immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology @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 = {Genome, RNA Interference, Animal, Cell Proliferation, Drosophila melanogaster/genetics/immunology/microbiology, Drosophila Proteins/genetics/metabolism, Epithelial Cells, Epithelial Cells/cytology/physiology, Genetically Modified, Genome, Hemocytes, Hemocytes/immunology/metabolism/microbiology, Homeostasis, Immunity, Innate, Innate/genetics, Insect, Intestinal Mucosa, Intestinal Mucosa/cytology/immunology/metabolism/microbiology, Janus Kinases, Janus Kinases/genetics/metabolism, Models, RNA Interference, Serratia Infections, Serratia Infections/genetics/immunology/microbiology, Serratia marcescens, Serratia marcescens/immunology/physiology, Signal Transduction, STAT Transcription Factors, STAT Transcription Factors/genetics/metabolism, Stem Cells, Stem Cells/cytology/physiology}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1126/science.1173164 Fermer
2007
Articles de journaux
6.	Ferrandon, Dominique; Gottar, Marie; Gobert, Vanessa [New mechanism for detection of infections using the innate immune system of animals] Article de journal Med Sci (Paris), 23 (8-9), p. 707–709, 2007, ISSN: 0767-0974. Liens \| BibTeX \| Étiquettes: Animal, Drosophila/immunology, Gram-Positive Bacteria, Gram-Positive Bacteria/pathogenicity, Gram-Positive Bacterial Infections, Gram-Positive Bacterial Infections/immunology, Humans, Immune System, Infection, Infection/diagnosis/immunology, Models @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 = {Animal, Drosophila/immunology, Gram-Positive Bacteria, Gram-Positive Bacteria/pathogenicity, Gram-Positive Bacterial Infections, Gram-Positive Bacterial Infections/immunology, Humans, Immune System, Infection, Infection/diagnosis/immunology, Models}, pubstate = {published}, tppubtype = {article} } Fermer doi:10.1051/medsci/20072389707 Fermer
5.	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 Article de journal PLoS Pathog., 3 (11), p. e173, 2007, ISSN: 1553-7374. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Disease Models, Electron, Fluorescence, Hemolymph, Host-Pathogen Interactions, Immunohistochemistry, Intestines, Microscopy, Reverse Transcriptase Polymerase Chain Reaction, Serratia Infections, Serratia marcescens, Transmission @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 = {Animal, Disease Models, Electron, Fluorescence, Hemolymph, Host-Pathogen Interactions, Immunohistochemistry, Intestines, Microscopy, Reverse Transcriptase Polymerase Chain Reaction, Serratia Infections, Serratia marcescens, Transmission}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1371/journal.ppat.0030173 Fermer
2003
Articles de journaux
4.	Hetru, Charles; Troxler, Laurent; Hoffmann, Jules A Drosophila melanogaster antimicrobial defense Article de journal J. Infect. Dis., 187 Suppl 2 , p. S327–334, 2003, ISSN: 0022-1899. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Bacterial Infections, bioinformatic, Immunity, Innate, Mycoses, Parasitic Diseases, Peptides, Signal Transduction @article{hetru_drosophila_2003, title = {Drosophila melanogaster antimicrobial defense}, author = { Charles Hetru and Laurent Troxler and Jules A. Hoffmann}, doi = {10.1086/374758}, issn = {0022-1899}, year = {2003}, date = {2003-06-01}, journal = {J. Infect. Dis.}, volume = {187 Suppl 2}, pages = {S327--334}, abstract = {The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides.}, keywords = {Animal, Bacterial Infections, bioinformatic, Immunity, Innate, Mycoses, Parasitic Diseases, Peptides, Signal Transduction}, pubstate = {published}, tppubtype = {article} } Fermer The Drosophila melanogaster host defense is complex but remarkably efficient. It is a multifaceted response to a variety of fungal, bacterial, and parasitic invaders. Current knowledge is discussed on recognition of infectious microorganisms and on the activation of intracellular signaling cascades that concur with the expression of numerous immune-responsive genes, among which, to date, the most prominent appear to encode potent antimicrobial peptides. Fermer doi:10.1086/374758 Fermer
3.	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 Article de journal Embo J, 22 , p. 1451–60, 2003, ISBN: 0261-4189. Résumé \| Liens \| BibTeX \| Étiquettes: Virulence, Animal, Caenorhabditis elegans/microbiology, Mutation, Non-U.S. Gov't, Serratia marcescens/genetics/pathogenicity, Support @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 = {Virulence, Animal, Caenorhabditis elegans/microbiology, Mutation, Non-U.S. Gov't, Serratia marcescens/genetics/pathogenicity, Support}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1093/emboj/cdg159 Fermer
2002
Articles de journaux
2.	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 Article de journal Nature, 416 , p. 640–644, 2002, ISBN: 0028-0836. Résumé \| Liens \| BibTeX \| Étiquettes: Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/immunology, Drosophila melanogaster/genetics/immunology/microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/immunology/physiology, Human, Insect/genetics, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't @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 = {Animal, Anti-Infective Agents/metabolism, Carrier Proteins/biosynthesis/genetics/immunology, Drosophila melanogaster/genetics/immunology/microbiology, Drosophila Proteins/genetics/metabolism, Epistasis, Female, Genes, Genetic, Genetic Predisposition to Disease, Gram-Negative Bacteria/immunology/physiology, Human, Insect/genetics, Messenger/genetics/metabolism, Mutation, Non-U.S. Gov't, P.H.S., Phenotype, RNA, Signal Transduction, Support, Survival Rate, Transgenes/genetics, U.S. Gov't}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer doi:10.1038/nature734 Fermer
2000
Articles de journaux
1.	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 Article de journal Immunity, 13 , p. 737–48., 2000, ISSN: 1074-7613. Résumé \| BibTeX \| Étiquettes: Genes, Animal, Anti-Infective Agents/immunology/metabolism, Drosophila/genetics/immunology, Gene Expression Regulation/immunology, Genes, Glycoside Hydrolases/immunology, Human, Insect, Insect Proteins/genetics/immunology, Non-U.S. Gov't, Organ Specificity, P.H.S., Reporter, Support, Transfection, U.S. Gov't @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 = {Genes, Animal, Anti-Infective Agents/immunology/metabolism, Drosophila/genetics/immunology, Gene Expression Regulation/immunology, Genes, Glycoside Hydrolases/immunology, Human, Insect, Insect Proteins/genetics/immunology, Non-U.S. Gov't, Organ Specificity, P.H.S., Reporter, Support, Transfection, U.S. Gov't}, pubstate = {published}, tppubtype = {article} } Fermer 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. Fermer

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