title: The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein.
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.
authors.affiliation: UPR 9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, F67084 Strasbourg, Cedex, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Gottar
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gobert
authors.forename: Tatiana
authors.initials: T
authors.lastname: Michel
authors.forename: Marcia
authors.initials: M
authors.lastname: Belvin
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Duyk
authors.forename: Jules A
authors.initials: JA
authors.lastname: Hoffmann
authors.forename: Dominique
authors.initials: D
authors.lastname: Ferrandon
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004843:Epistasis, Genetic; D005260:Female; D017344:Genes, Insect / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006090:Gram-Negative Bacteria / Q000276:immunology* / Q000502:physiology; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; C118897:peptidoglycan recognition protein