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.
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.
UPR9022 du CNRS, Université de Strasbourg, Equipe Fondation Recherche Médicale, Institut de Biologie Moleculaire et Cellulaire, 15 rue R. Descartes, 67084 Strasbourg Cedex, France.
Arshad
A
Ayyaz
Philippe
P
Giammarinaro
Samuel
S
Liégeois
Matthieu
M
Lestradet
Dominique
D
Ferrandon
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004331:Drosophila melanogaster; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007410:Intestinal Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009154:Mutation; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013203:Staphylococcal Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013210:Staphylococcus / Q000276:immunology*; D013217:Starvation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D029721:Drosophila Proteins; C499312:Myd88 protein, Drosophila; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors