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2011
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
In: PLoS ONE, vol. 6, no. 3, pp. e14743, 2011, ISSN: 1932-6203.
Abstract | Links | BibTeX | Tags: 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}
}
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.
2009
Shia Alice K H, Glittenberg Marcus, Thompson Gavin, Weber Alexander N R, Reichhart Jean-Marc, Ligoxygakis Petros
Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes Journal Article
In: J. Cell. Sci., vol. 122, no. Pt 24, pp. 4505–4515, 2009, ISSN: 1477-9137.
Abstract | Links | BibTeX | Tags: Animals, Enterococcus faecalis, Escherichia coli, Fat Body, Hemocytes, Larva, M3i, reichhart, Toll-Like Receptors
@article{shia_toll-dependent_2009,
title = {Toll-dependent antimicrobial responses in Drosophila larval fat body require Spätzle secreted by haemocytes},
author = {Alice K H Shia and Marcus Glittenberg and Gavin Thompson and Alexander N R Weber and Jean-Marc Reichhart and Petros Ligoxygakis},
doi = {10.1242/jcs.049155},
issn = {1477-9137},
year = {2009},
date = {2009-12-01},
journal = {J. Cell. Sci.},
volume = {122},
number = {Pt 24},
pages = {4505--4515},
abstract = {In Drosophila, the humoral response characterised by the synthesis of antimicrobial peptides (AMPs) in the fat body (the equivalent of the mammalian liver) and the cellular response mediated by haemocytes (blood cells) engaged in phagocytosis represent two major reactions that counter pathogens. Although considerable analysis has permitted the elucidation of mechanisms pertaining to the two responses individually, the mechanism of their coordination has been unclear. To characterise the signals with which infection might be communicated between blood cells and fat body, we ablated circulating haemocytes and defined the parameters of AMP gene activation in larvae. We found that targeted ablation of blood cells influenced the levels of AMP gene expression in the fat body following both septic injury and oral infection. Expression of the AMP gene drosomycin (a Toll target) was blocked when expression of the Toll ligand Spätzle was knocked down in haemocytes. These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.},
keywords = {Animals, Enterococcus faecalis, Escherichia coli, Fat Body, Hemocytes, Larva, M3i, reichhart, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
In Drosophila, the humoral response characterised by the synthesis of antimicrobial peptides (AMPs) in the fat body (the equivalent of the mammalian liver) and the cellular response mediated by haemocytes (blood cells) engaged in phagocytosis represent two major reactions that counter pathogens. Although considerable analysis has permitted the elucidation of mechanisms pertaining to the two responses individually, the mechanism of their coordination has been unclear. To characterise the signals with which infection might be communicated between blood cells and fat body, we ablated circulating haemocytes and defined the parameters of AMP gene activation in larvae. We found that targeted ablation of blood cells influenced the levels of AMP gene expression in the fat body following both septic injury and oral infection. Expression of the AMP gene drosomycin (a Toll target) was blocked when expression of the Toll ligand Spätzle was knocked down in haemocytes. These results show that in larvae, integration of the two responses in a systemic reaction depend on the production of a cytokine (spz), a process that strongly parallels the mammalian immune response.
2002
Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections Journal Article
In: Nature Immunology, vol. 3, no. 1, pp. 91–97, 2002, ISSN: 1529-2908.
Abstract | Links | BibTeX | Tags: Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection
@article{tauszig-delamasure_drosophila_2002,
title = {Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections},
author = {Servane Tauszig-Delamasure and Hana Bilak and Maria Capovilla and Jules A Hoffmann and Jean-Luc Imler},
doi = {10.1038/ni747},
issn = {1529-2908},
year = {2002},
date = {2002-01-01},
journal = {Nature Immunology},
volume = {3},
number = {1},
pages = {91--97},
abstract = {We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.},
keywords = {Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection},
pubstate = {published},
tppubtype = {article}
}
We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.
2001
Michel T, Reichhart Jean-Marc, Hoffmann Jules A, Royet Julien
Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein Journal Article
In: Nature, vol. 414, no. 6865, pp. 756–759, 2001, ISSN: 0028-0836.
Abstract | Links | BibTeX | Tags: Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors
@article{michel_drosophila_2001,
title = {Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein},
author = {T Michel and Jean-Marc Reichhart and Jules A Hoffmann and Julien Royet},
doi = {10.1038/414756a},
issn = {0028-0836},
year = {2001},
date = {2001-12-01},
journal = {Nature},
volume = {414},
number = {6865},
pages = {756--759},
abstract = {Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.},
keywords = {Amino Acid, Animals, Anti-Bacterial Agents, Anti-Infective Agents, Bacillus thuringiensis, Carrier Proteins, Cell Surface, Chromosome Mapping, Enterococcus faecalis, Fungi, Genes, Gram-Positive Bacteria, Hemolymph, hoffmann, Humans, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Mutation, Receptors, reichhart, Sequence Homology, Toll-Like Receptors},
pubstate = {published},
tppubtype = {article}
}
Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.