Publications
2018
Ferreira Flávia Viana, Aguiar Eric Roberto Guimarães Rocha, Olmo Roenick Proveti, de Oliveira Karla Pollyanna Vieira, Silva Emanuele Guimarães, Sant'Anna Maurício Roberto Viana, de Gontijo Nelder Figueiredo, Kroon Erna Geessien, Imler Jean-Luc, Marques João Trindade
The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis Article de journal
Dans: PLoS Negl Trop Dis, vol. 12, no. 6, p. e0006569, 2018, ISSN: 1935-2735.
Résumé | Liens | BibTeX | Étiquettes: Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral
@article{ferreira_small_2018,
title = {The small non-coding RNA response to virus infection in the Leishmania vector Lutzomyia longipalpis},
author = {Flávia Viana Ferreira and Eric Roberto Guimarães Rocha Aguiar and Roenick Proveti Olmo and Karla Pollyanna Vieira de Oliveira and Emanuele Guimarães Silva and Maurício Roberto Viana Sant'Anna and Nelder Figueiredo de Gontijo and Erna Geessien Kroon and Jean-Luc Imler and João Trindade Marques},
doi = {10.1371/journal.pntd.0006569},
issn = {1935-2735},
year = {2018},
date = {2018-01-01},
journal = {PLoS Negl Trop Dis},
volume = {12},
number = {6},
pages = {e0006569},
abstract = {Sandflies are well known vectors for Leishmania but also transmit a number of arthropod-borne viruses (arboviruses). Few studies have addressed the interaction between sandflies and arboviruses. RNA interference (RNAi) mechanisms utilize small non-coding RNAs to regulate different aspects of host-pathogen interactions. The small interfering RNA (siRNA) pathway is a broad antiviral mechanism in insects. In addition, at least in mosquitoes, another RNAi mechanism mediated by PIWI interacting RNAs (piRNAs) is activated by viral infection. Finally, endogenous microRNAs (miRNA) may also regulate host immune responses. Here, we analyzed the small non-coding RNA response to Vesicular stomatitis virus (VSV) infection in the sandfly Lutzoymia longipalpis. We detected abundant production of virus-derived siRNAs after VSV infection in adult sandflies. However, there was no production of virus-derived piRNAs and only mild changes in the expression of vector miRNAs in response to infection. We also observed abundant production of virus-derived siRNAs against two other viruses in Lutzomyia Lulo cells. Together, our results suggest that the siRNA but not the piRNA pathway mediates an antiviral response in sandflies. In agreement with this hypothesis, pre-treatment of cells with dsRNA against VSV was able to inhibit viral replication while knock-down of the central siRNA component, Argonaute-2, led to increased virus levels. Our work begins to elucidate the role of RNAi mechanisms in the interaction between L. longipalpis and viruses and should also open the way for studies with other sandfly-borne pathogens.},
keywords = {Animals, Host-Pathogen Interactions, imler, Insect Vectors, Leishmania, M3i, ncRNA, Psychodidae, RNA, RNA Interference, Small Interfering, Untranslated, Vesicular stomatitis Indiana virus, Viral},
pubstate = {published},
tppubtype = {article}
}
2014
Lamiable Olivier, Imler Jean-Luc
Induced antiviral innate immunity in Drosophila Article de journal
Dans: Current Opinion in Microbiology, vol. 20, p. 62–68, 2014, ISSN: 1879-0364.
Résumé | Liens | BibTeX | Étiquettes: Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction
@article{lamiable_induced_2014,
title = {Induced antiviral innate immunity in Drosophila},
author = {Olivier Lamiable and Jean-Luc Imler},
doi = {10.1016/j.mib.2014.05.006},
issn = {1879-0364},
year = {2014},
date = {2014-08-01},
journal = {Current Opinion in Microbiology},
volume = {20},
pages = {62--68},
abstract = {Immunity to viral infections in the model organism Drosophila melanogaster involves both RNA interference and additional induced responses. The latter include not only cellular mechanisms such as programmed cell death and autophagy, but also the induction of a large set of genes, some of which contribute to the control of viral replication and resistance to infection. This induced response to infection is complex and involves both virus-specific and cell-type specific mechanisms. We review here recent developments, from the sensing of viral infection to the induction of signaling pathways and production of antiviral effector molecules. Our current understanding, although still partial, validates the Drosophila model of antiviral induced immunity for insect pests and disease vectors, as well as for mammals.},
keywords = {Animals, Gene Expression Regulation, Host-Pathogen Interactions, imler, Immunity, Innate, M3i, RNA Viruses, Signal Transduction},
pubstate = {published},
tppubtype = {article}
}
Haller Samantha, Limmer Stefanie, Ferrandon Dominique
Assessing Pseudomonas virulence with a nonmammalian host: Drosophila melanogaster Article de journal
Dans: Methods Mol. Biol., vol. 1149, p. 723–740, 2014, ISSN: 1940-6029.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Antimicrobial Cationic Peptides, Biological Assay, Colony Count, Disease Models, ferrandon, Hemolymph, Host-Pathogen Interactions, M3i, 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, Animals, Antimicrobial Cationic Peptides, Biological Assay, Colony Count, Disease Models, ferrandon, Hemolymph, Host-Pathogen Interactions, M3i, Mammals, Microbial, Pseudomonas aeruginosa, Pseudomonas Infections, Reverse Transcriptase Polymerase Chain Reaction, Virulence},
pubstate = {published},
tppubtype = {article}
}
Lestradet Matthieu, Lee Kwan Zin, Ferrandon Dominique
Drosophila as a model for intestinal infections Article de journal
Dans: Methods Mol Biol, vol. 1197, p. 11–40, 2014, ISSN: 1940-6029 (Electronic) 1064-3745 (Linking).
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacterial Physiological Phenomena, Disease Models, ferrandon, Gastrointestinal Tract, Host-Pathogen Interactions, M3i
@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, Animals, Bacterial Physiological Phenomena, Disease Models, ferrandon, Gastrointestinal Tract, Host-Pathogen Interactions, M3i},
pubstate = {published},
tppubtype = {article}
}
2013
Fukuyama Hidehiro, Verdier Yann, Guan Yongsheng, Makino-Okamura Chieko, Shilova Victoria, Liu Xi, Maksoud Elie, Matsubayashi Jun, Haddad Iman, Spirohn Kerstin, Ono Kenichiro, Hetru Charles, Rossier Jean, Ideker Trey, Boutros Michael, Vinh Joëlle, Hoffmann Jules A
Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge Article de journal
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 110, no. 26, p. 10717–10722, 2013, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier
@article{fukuyama_landscape_2013,
title = {Landscape of protein-protein interactions in Drosophila immune deficiency signaling during bacterial challenge},
author = {Hidehiro Fukuyama and Yann Verdier and Yongsheng Guan and Chieko Makino-Okamura and Victoria Shilova and Xi Liu and Elie Maksoud and Jun Matsubayashi and Iman Haddad and Kerstin Spirohn and Kenichiro Ono and Charles Hetru and Jean Rossier and Trey Ideker and Michael Boutros and Joëlle Vinh and Jules A Hoffmann},
doi = {10.1073/pnas.1304380110},
issn = {1091-6490},
year = {2013},
date = {2013-06-01},
journal = {Proc. Natl. Acad. Sci. U.S.A.},
volume = {110},
number = {26},
pages = {10717--10722},
abstract = {The Drosophila defense against pathogens largely relies on the activation of two signaling pathways: immune deficiency (IMD) and Toll. The IMD pathway is triggered mainly by Gram-negative bacteria, whereas the Toll pathway responds predominantly to Gram-positive bacteria and fungi. The activation of these pathways leads to the rapid induction of numerous NF-κB-induced immune response genes, including antimicrobial peptide genes. The IMD pathway shows significant similarities with the TNF receptor pathway. Recent evidence indicates that the IMD pathway is also activated in response to various noninfectious stimuli (i.e., inflammatory-like reactions). To gain a better understanding of the molecular machinery underlying the pleiotropic functions of this pathway, we first performed a comprehensive proteomics analysis to identify the proteins interacting with the 11 canonical members of the pathway initially identified by genetic studies. We identified 369 interacting proteins (corresponding to 291 genes) in heat-killed Escherichia coli-stimulated Drosophila S2 cells, 92% of which have human orthologs. A comparative analysis of gene ontology from fly or human gene annotation databases points to four significant common categories: (i) the NuA4, nucleosome acetyltransferase of H4, histone acetyltransferase complex, (ii) the switching defective/sucrose nonfermenting-type chromatin remodeling complex, (iii) transcription coactivator activity, and (iv) translation factor activity. Here we demonstrate that sumoylation of the IκB kinase homolog immune response-deficient 5 plays an important role in the induction of antimicrobial peptide genes through a highly conserved sumoylation consensus site during bacterial challenge. Taken together, the proteomics data presented here provide a unique avenue for a comparative functional analysis of proteins involved in innate immune reactions in flies and mammals.},
keywords = {Amino Acid, Animals, Chromatin Assembly and Disassembly, Escherichia coli, functional proteomics, Genes, Genetically Modified, Histone Acetyltransferases, hoffmann, Host-Pathogen Interactions, Humans, IMD interactome, Insect, M3i, Models, Molecular, Protein Interaction Maps, Sequence Homology, Signal Transduction, small ubiquitin-like modifier},
pubstate = {published},
tppubtype = {article}
}
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
Dans: Cell Host Microbe, vol. 13, no. 5, p. 570–583, 2013, ISSN: 1934-6069.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, 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, M3i, Protein Binding, Protein Interaction Mapping, reichhart, 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, Animals, 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, M3i, Protein Binding, Protein Interaction Mapping, reichhart, Salmonella typhimurium, Sequence Analysis, Shigella flexneri, Virulence Factors},
pubstate = {published},
tppubtype = {article}
}
2011
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
Dans: Proc. Natl. Acad. Sci. U.S.A., vol. 108, no. 42, p. 17378–17383, 2011, ISSN: 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, 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, Animals, Bacteremia, Bacterial Proteins, Cellular, Disease Models, ferrandon, Genes, Genetically Modified, Hemolymph, Host-Pathogen Interactions, Immunity, Insect, M3i, Mutation, Oral, Pseudomonas aeruginosa, Pseudomonas Infections, Quorum Sensing, Trans-Activators, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
Chtarbanova Stanislava, Imler Jean-Luc
Microbial sensing by Toll receptors: a historical perspective Article de journal
Dans: Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 31, no. 8, p. 1734–1738, 2011, ISSN: 1524-4636.
Résumé | Liens | BibTeX | Étiquettes: Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors
@article{chtarbanova_microbial_2011,
title = {Microbial sensing by Toll receptors: a historical perspective},
author = {Stanislava Chtarbanova and Jean-Luc Imler},
doi = {10.1161/ATVBAHA.108.179523},
issn = {1524-4636},
year = {2011},
date = {2011-08-01},
journal = {Arteriosclerosis, Thrombosis, and Vascular Biology},
volume = {31},
number = {8},
pages = {1734--1738},
abstract = {The family of Toll-like receptors plays an essential role in the induction of the immune response. These receptors sense the presence of microbial ligands and activate the nuclear factor-κB transcription factor. We review the key studies that led from the formulation of the concept of pattern recognition receptors to the characterization of Toll-like receptors, insisting on the important role played by the model organism Drosophila melanogaster and on the increasing evidence connecting these receptors to cardiovascular disease.},
keywords = {Animals, Cardiovascular Diseases, history, Host-Pathogen Interactions, Humans, imler, Immunity, Innate, M3i, Macrophages, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
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
Dans: Curr Drug Targets, vol. 12, no. 7, p. 978–999, 2011, ISSN: 1873-5592.
Résumé | BibTeX | Étiquettes: Animal, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, 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, Animals, Anti-Infective Agents, Disease Models, Drug Delivery Systems, Drug Design, Drug Resistance, ferrandon, Fungi, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, M3i, Microbial, Pseudomonas aeruginosa},
pubstate = {published},
tppubtype = {article}
}
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 Article de journal
Dans: PLoS ONE, vol. 6, no. 3, p. e14743, 2011, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus
@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 = {Animals, Antimicrobial Cationic Peptides, Carrier Proteins, Cell Surface, Cellular, Enterococcus faecalis, ferrandon, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Host-Pathogen Interactions, Humoral, Immunity, Innate, M3i, Micrococcus luteus, Opsonin Proteins, Phagocytosis, Receptors, Signal Transduction, Solubility, Staphylococcus aureus},
pubstate = {published},
tppubtype = {article}
}
2009
Ferrandon Dominique
Host tolerance versus resistance and microbial virulence in the host-pathogen equation Article de journal
Dans: Cell Host Microbe, vol. 6, no. 3, p. 203–205, 2009, ISSN: 1934-6069.
Résumé | Liens | BibTeX | Étiquettes: Animals, ferrandon, Host-Pathogen Interactions, Immune Tolerance, M3i, Salmonella typhimurium, Virulence
@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 = {Animals, ferrandon, Host-Pathogen Interactions, Immune Tolerance, M3i, Salmonella typhimurium, Virulence},
pubstate = {published},
tppubtype = {article}
}
Kemp Cordula, Imler Jean-Luc
Antiviral immunity in drosophila Article de journal
Dans: Current Opinion in Immunology, vol. 21, no. 1, p. 3–9, 2009, ISSN: 1879-0372.
Résumé | Liens | BibTeX | Étiquettes: Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence
@article{kemp_antiviral_2009,
title = {Antiviral immunity in drosophila},
author = {Cordula Kemp and Jean-Luc Imler},
doi = {10.1016/j.coi.2009.01.007},
issn = {1879-0372},
year = {2009},
date = {2009-02-01},
journal = {Current Opinion in Immunology},
volume = {21},
number = {1},
pages = {3--9},
abstract = {Genetic analysis of the drosophila antiviral response indicates that RNA interference plays a major role. This contrasts with the situation in mammals, where interferon-induced responses mediate innate antiviral host-defense. An inducible response also contributes to antiviral immunity in drosophila, and similarities in the sensing and signaling of viral infection are becoming apparent between drosophila and mammals. In particular, DExD/H box helicases appear to play a crucial role in the cytosolic detection of viral RNAs in flies and mammals.},
keywords = {Animals, Argonaute Proteins, Caspases, DEAD-box RNA Helicases, Evolution, Gene Expression Regulation, Host-Pathogen Interactions, imler, M3i, Membrane Proteins, Molecular, Nuclear Proteins, Ribonuclease III, RNA, RNA Helicases, RNA Interference, RNA Virus Infections, RNA Viruses, RNA-Induced Silencing Complex, Viral, Virulence},
pubstate = {published},
tppubtype = {article}
}
2008
Huszar Tünde, Imler Jean-Luc
Drosophila viruses and the study of antiviral host-defense Article de journal
Dans: Advances in Virus Research, vol. 72, p. 227–265, 2008, ISSN: 0065-3527.
Résumé | Liens | BibTeX | Étiquettes: Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses
@article{huszar_drosophila_2008,
title = {Drosophila viruses and the study of antiviral host-defense},
author = {Tünde Huszar and Jean-Luc Imler},
doi = {10.1016/S0065-3527(08)00406-5},
issn = {0065-3527},
year = {2008},
date = {2008-01-01},
journal = {Advances in Virus Research},
volume = {72},
pages = {227--265},
abstract = {The fruit fly Drosophila melanogaster is a powerful model to study host-pathogen interactions. Most studies so far have focused on extracellular pathogens such as bacteria and fungi. More recently, viruses have come to the front, and RNA interference was shown to play a critical role in the control of viral infections in drosophila. We review here our current knowledge on drosophila viruses. A diverse set of RNA viruses belonging to several families (Rhabdoviridae, Dicistroviridae, Birnaviridae, Reoviridae, Errantiviridae) has been reported in D. melanogaster. By contrast, no DNA virus has been recovered up to now. The drosophila viruses represent powerful tools to study virus-cell interactions in vivo. Analysis of the literature however reveals that for many of them, important gaps exist in our understanding of their replication cycle, genome organization, morphology or pathogenesis. The data obtained in the past few years on antiviral defense mechanisms in drosophila, which point to evolutionary conserved pathways, highlight the potential of the D. melanogaster model to study antiviral innate immunity and to better understand the complex interaction between arthropod-borne viruses and their insect vectors.},
keywords = {Animals, Host-Pathogen Interactions, imler, Immunity, Innate, Insect Viruses, M3i, RNA Interference, RNA Viruses},
pubstate = {published},
tppubtype = {article}
}
2007
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
Dans: PLoS Pathog., vol. 3, no. 11, p. e173, 2007, ISSN: 1553-7374.
Résumé | Liens | BibTeX | Étiquettes: Animal, Animals, Disease Models, Electron, ferrandon, fluorescence, Hemolymph, hoffmann, Host-Pathogen Interactions, Immunohistochemistry, Intestines, M3i, 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, Animals, Disease Models, Electron, ferrandon, fluorescence, Hemolymph, hoffmann, Host-Pathogen Interactions, Immunohistochemistry, Intestines, M3i, Microscopy, Reverse Transcriptase Polymerase Chain Reaction, Serratia Infections, Serratia marcescens, Transmission},
pubstate = {published},
tppubtype = {article}
}