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^1,2. 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^{3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18}. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections^3,9. 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)⁶. PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members^{19,20,21,22,23}. 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.