RRC ID 30675
Author Gottar M, Gobert V, Michel T, Belvin M, Duyk G, Hoffmann JA, Ferrandon D, Royet J.
Title The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein.
Journal Nature
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.
Volume 416(6881)
Pages 640-4
Published 2002-4-11
DOI 10.1038/nature734
PII nature734
PMID 11912488
MeSH Animals Anti-Bacterial Agents / metabolism Carrier Proteins / biosynthesis Carrier Proteins / genetics Carrier Proteins / immunology* Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / immunology* Drosophila melanogaster / microbiology* Epistasis, Genetic Female Genes, Insect / genetics Genetic Predisposition to Disease Gram-Negative Bacteria / immunology* Gram-Negative Bacteria / physiology Humans Mutation Phenotype RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction Survival Rate Transgenes / genetics
IF 42.779
Times Cited 453