Relations Hôte-Pathogène et Résilience

@article{Y2024,

title = {Perturbation of METTL1-mediated tRNA N7-methylguanosine modification induces senescence and aging},

author = {Fu Y AND Jiang F and Zhang X and Pan Y and Xu R AND Liang X AND Wu X AND Li X AND Lin K AND Shi R AND Zhang X AND Ferrandon D AND Liu J AND Pei D AND Wang J AND Wang T},

doi = {10.1038/s41467-024-49796-8},

year  = {2024},

date = {2024-07-08},

journal = {Nature Communications},

volume = {8},

number = {1},

issue = {15},

pages = {5713},

abstract = {Cellular senescence is characterized by a decrease in protein synthesis, although the underlying processes are mostly unclear. Chemical modifications to transfer RNAs (tRNAs) frequently influence tRNA activity, which is crucial for translation. We describe how tRNA N7-methylguanosine (m7G46) methylation, catalyzed by METTL1-WDR4, regulates translation and influences senescence phenotypes. Mettl1/Wdr4 and m7G gradually diminish with senescence and aging. A decrease in METTL1 causes a reduction in tRNAs, especially those with the m7G modification, via the rapid tRNA degradation (RTD) pathway. The decreases cause ribosomes to stall at certain codons, impeding the translation of mRNA that is essential in pathways such as Wnt signaling and ribosome biogenesis. Furthermore, chronic ribosome stalling stimulates the ribotoxic and integrative stress responses, which induce senescence-associated secretory phenotype. Moreover, restoring eEF1A protein mitigates senescence phenotypes caused by METTL1 deficiency by reducing RTD. Our findings demonstrate that tRNA m7G modification is essential for preventing premature senescence and aging by enabling efficient mRNA translation.},

keywords = {ferrandon, Gene Expression, M3i, RNA, Senescence},

pubstate = {published},

tppubtype = {article}

}

@article{J2024,

title = {A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster host},

author = {Chen J and Lin G and Ma K and Li Z and Liégeois S and Ferrandon D},

editor = {. . PLoS Pathog. 2024 Jun 4;20(6):e1012252. . eCollection 2024 Ju},

doi = {doi: 10.1371/journal.ppat.1012252},

year  = {2024},

date = {2024-06-04},

urldate = {2024-06-04},

journal = {PLoS Pathog.},

abstract = {Microbial pathogenicity often depends on the route of infection. For instance, P. aeruginosa or S. marcescens cause acute systemic infections when low numbers of bacteria are injected into D. melanogaster flies whereas flies succumb much slower to the continuous ingestion of these pathogens, even though both manage to escape from the gut compartment and reach the hemocoel. Here, we have developed a latent P. aeruginosa infection model by feeding flies on the bacteria for a short period. The bacteria stably colonize internal tissues yet hardly cause any damage since latently-infected flies live almost as long as noninfected control flies. The apparently dormant bacteria display particular characteristics in terms of bacterial colony morphology, composition of the outer cell wall, and motility. The virulence of these bacteria can however be reactivated upon wounding the host. We show that melanization but not the cellular or the systemic humoral response is the predominant host defense that establishes latency and may coerce the bacteria to a dormant state. In addition, the lasting activation of the melanization responses in latently-infected flies provides a degree of protection to the host against a secondary fungal infection. Latent infection by an ingested pathogen protects against a variety of homologous or heterologous systemic secondary infectious challenges, a situation previously described for the endosymbiotic Wolbachia bacteria, a guard against viral infections.},

keywords = {Drosophila melanogaster, ferrandon, Innate immune response, M3i, Pseudomonas aeruginosa},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2023,

title = {A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium},

author = {Jianqiong Huang and Yanyan Lou and Jiyong Liu and Philippe Bulet and Chuping Cai and Kaiyu Ma and Renjie Jiao and Jules A Hoffmann and Samuel Liégeois and Zi Lia and Dominique Ferrandon},

editor = {Hugo Bellen, Baylor College of Medicine, Houston, TX},

url = {https://doi.org/10.1073/pnas.2205140120},

doi = {10.1073/pnas.2205140120},

year  = {2023},

date = {2023-03-14},

urldate = {2023-03-14},

journal = {PNAS},

volume = {120},

number = {12},

abstract = {Major immune response pathways control the expression of hundreds of genes that represent potential effectors of the immune response. The Drosophila Toll pathway is required in the host defenses against several Gram-positive bacterial infections as well as against fungal infections. The current paradigm is that peptides secreted in the hemolymph during the systemic immune response are either bona fide antimicrobial peptides or likely ones. The finding of a dual role for one Toll pathway effector in the resilience to both Enterococcus faecalis and Metarhizium robertsii infections underscores an original concept in insect innate immunity. Evolution can select effectors tailored to protect the host from the action of microbial toxins of prokaryotic or eukaryotic origin, independently of antibodies or detoxification pathways.},

keywords = {Baramicin A, Destruxin A, disease tolerance, enterocin O16, ferrandon, hoffmann, M3i, microbial toxins, resilience},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36322050,

title = {The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins},

author = {Rui Xu and Yanyan Lou and Antonin Tidu and Philippe Bulet and Thorsten Heinekamp and Franck Martin and Axel Brakhage and Zi Li and Samuel Liégeois and Dominique Ferrandon},

url = {https://pubmed.ncbi.nlm.nih.gov/36322050/},

doi = {10.15252/embr.202256036},

issn = {1469-3178},

year  = {2022},

date = {2022-11-01},

urldate = {2022-11-01},

journal = {EMBO Rep},

pages = {e56036},

abstract = {Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus are susceptible to the injection of two Aspergillus mycotoxins, restrictocin and verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins is rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 is expressed in the nervous system exhibit an enhanced recovery from the tremors induced by injected verruculogen and display improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increases its resilience to infection.},

keywords = {ERIANI, ferrandon, M3i, MARTIN, Unité ARN},

pubstate = {published},

tppubtype = {article}

}

@article{Liégeois2020b,

title = {An atlas for hemocytes in an insect},

author = {Samuel Liégeois and Dominique Ferrandon},

editor = {Elife},

url = {https://elifesciences.org/articles/59113},

doi = {10.7554/eLife.59113},

year  = {2020},

date = {2020-06-30},

journal = {Elife},

abstract = {Single-cell RNA sequencing has revealed distinct subpopulations of hemocytes in fruit fly larvae},

keywords = {Drosophila, ferrandon, Hemocytes, M3i, single-cell},

pubstate = {published},

tppubtype = {article}

}

@article{Franchet2019,

title = {Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies},

author = {Adrien Franchet and Sebastian Niehus and Gaetan Caravello and Dominique Ferrandon},

editor = {Nature Publishing Group},

url = {https://www.nature.com/articles/s41564-018-0344-y},

doi = {10.1038/s41564-018-0344-y},

isbn = {2058-5276},

year  = {2019},

date = {2019-01-28},

journal = {Nature Microbiology},

volume = {4},

number = {4},

pages = {645},

abstract = {A Drosophila melanogaster systemic infection model for the microsporidian Tubulinosema ratisbonensis reveals that the parasite hijacks host phosphatidic acid, which is a limiting precursor for synthesis of parasite membranes and therefore proliferation.},

keywords = {Drosophila, ferrandon, Host-Parasite Interactions, Lipids, M3i, metabolism, microsporidia},

pubstate = {published},

tppubtype = {article}

}

@article{S2018,

title = {Quorum-sensing regulator RhlR but not its autoinducer RhlI enables Pseudomonas to evade opsonization},

author = {Samantha Haller and Adrien Franchet and A Hakkim and J Chen and E Drenkard and S Yu and Steffi Schirmeier and Zi Li and Nelson Martins and FM Ausubel and Samuel Liégeois and Dominique Ferrandon},

url = {http://embor.embopress.org/content/early/2018/03/09/embr.201744880},

doi = {10.15252/embr.201744880},

year  = {2018},

date = {2018-03-09},

journal = {EMBO Reports},

keywords = {Drosophila, ferrandon, M3i, Opsonin Proteins, Phagocytosis, Pseudomonas aeruginosa, Quorum Sensing},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2016,

title = {Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut Epithelium to Pore-Forming Toxin Attack},

author = {Kwang-Zin Lee and Matthieu Lestradet and Catherine Socha and Stefanie Schirmeier and Antonin Schmitz and Caroline Spenlé and Olivier Lefebvre and Céline Keime and Wennida M. Yamba and Richard Bou Aoun and Samuel Liegeois and Yannick Schwab and Patricia Simon-Assmann and Frédéric Dalle and Dominique Ferrandon},

editor = {L Abate},

url = {http://www.sciencedirect.com/science/article/pii/S193131281630436X},

doi = {10.1016/j.chom.2016.10.010},

issn = {1931-3128},

year  = {2016},

date = {2016-11-23},

urldate = {2016-11-25},

journal = {Cell Host & Microbe},

abstract = {Summary 

Besides digesting nutrients, the gut protects the host against invasion by pathogens. Enterocytes may be subjected to damage by both microbial and host defensive responses, causing their death. Here, we report a rapid epithelial response that alleviates infection stress and protects the enterocytes from the action of microbial virulence factors. Intestinal epithelia exposed to hemolysin, a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily conserved process of thinning followed by the recovery of their initial thickness within a few hours. In response to hemolysin attack, Drosophila melanogaster enterocytes extrude most of their apical cytoplasm, including damaged organelles such as mitochondria, yet do not lyse. We identify two secreted peptides, the expression of which requires CyclinJ, that mediate the recovery phase in which enterocytes regain their original shape and volume. Epithelial thinning and recovery constitute a fast and efficient response to intestinal infections, with pore-forming toxins acting as alarm signals.},

keywords = {Epithelium, ferrandon, gut, M3i, resilience},

pubstate = {published},

tppubtype = {article}

}

@article{brunke_mice_2015b,

title = {Of mice, flies--and men? Comparing fungal infection models for large-scale screening efforts},

author = {Sascha Brunke and Jessica Quintin and Lydia Kasper and Ilse D Jacobsen and Martin E Richter and Ekkehard Hiller and Tobias Schwarzmüller and Christophe d'Enfert and Karl Kuchler and Steffen Rupp and Bernhard Hube and Dominique Ferrandon},

url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415897/},

doi = {10.1242/dmm.019901},

issn = {1754-8411},

year  = {2015},

date = {2015-01-01},

journal = {Dis Model Mech},

volume = {8},

number = {5},

pages = {473--486},

abstract = {Studying infectious diseases requires suitable hosts for experimental in vivo infections. Recent years have seen the advent of many alternatives to murine infection models. However, the use of non-mammalian models is still controversial because it is often unclear how well findings from these systems predict virulence potential in humans or other mammals. Here, we compare the commonly used models, fruit fly and mouse (representing invertebrate and mammalian hosts), for their similarities and degree of correlation upon infection with a library of mutants of an important fungal pathogen, the yeast Candida glabrata. Using two indices, for fly survival time and for mouse fungal burden in specific organs, we show a good agreement between the models. We provide a suitable predictive model for estimating the virulence potential of C. glabrata mutants in the mouse from fly survival data. As examples, we found cell wall integrity mutants attenuated in flies, and mutants of a MAP kinase pathway had defective virulence in flies and reduced relative pathogen fitness in mice. In addition, mutants with strongly reduced in vitro growth generally, but not always, had reduced virulence in flies. Overall, we demonstrate that surveying Drosophila survival after infection is a suitable model to predict the outcome of murine infections, especially for severely attenuated C. glabrata mutants. Pre-screening of mutants in an invertebrate Drosophila model can, thus, provide a good estimate of the probability of finding a strain with reduced microbial burden in the mouse host.},

keywords = {Alternative infection models, Candida glabrata, ferrandon, Fungal virulence factors, M3i, Mutant library, Signature-tagged mutagenesis},

pubstate = {published},

tppubtype = {article}

}

@article{amcheslavsky_enteroendocrine_2014b,

title = {Enteroendocrine cells support intestinal stem-cell-mediated homeostasis in Drosophila},

author = {Alla Amcheslavsky and Wei Song and Qi Li and Yingchao Nie and Ivan Bragatto and Dominique Ferrandon and Norbert Perrimon and Tony Y Ip},

doi = {10.1016/j.celrep.2014.08.052},

issn = {2211-1247},

year  = {2014},

date = {2014-10-01},

journal = {Cell Rep},

volume = {9},

number = {1},

pages = {32--39},

abstract = {Intestinal stem cells in the adult Drosophila midgut are regulated by growth factors produced from the surrounding niche cells including enterocytes and visceral muscle. The role of the other major cell type, the secretory enteroendocrine cells, in regulating intestinal stem cells remains unclear. We show here that newly eclosed scute loss-of-function mutant flies are completely devoid of enteroendocrine cells. These enteroendocrine cell-less flies have normal ingestion and fecundity but shorter lifespan. Moreover, in these newly eclosed mutant flies, the diet-stimulated midgut growth that depends on the insulin-like peptide 3 expression in the surrounding muscle is defective. The depletion of Tachykinin-producing enteroendocrine cells or knockdown of Tachykinin leads to a similar although less severe phenotype. These results establish that enteroendocrine cells serve as an important link between diet and visceral muscle expression of an insulin-like growth factor to stimulate intestinal stem cell proliferation and tissue growth.},

keywords = {Animals, Cell Differentiation, Enterocytes, Enteroendocrine Cells, Female, ferrandon, Homeostasis, Intestines, M3i, Male, Stem Cells, Tachykinins},

pubstate = {published},

tppubtype = {article}

}