RRC ID 1791
Author Pili-Floury S, Leulier F, Takahashi K, Saigo K, Samain E, Ueda R, Lemaitre B.
Title In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults.
Journal J. Biol. Chem.
Abstract The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions via the selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist Gram-negative bacterial infection. Microbial recognition is achieved through peptidoglycan recognition proteins (PGRPs); Gram-positive bacteria activate the Toll pathway through a circulating PGRP (PGRP-SA), and Gram-negative bacteria activate the Imd pathway via PGRP-LC, a putative transmembrane receptor, and PGRP-LE. Gram-negative binding proteins (GNBPs) were originally identified in Bombyx mori for their capacity to bind various microbial compounds. Three GNBPs and two related proteins are encoded in the Drosophila genome, but their function is not known. Using inducible expression of GNBP1 double-stranded RNA, we now demonstrate that GNBP1 is required for Toll activation in response to Gram-positive bacterial infection; GNBP1 double-stranded RNA expression renders flies susceptible to Gram-positive bacterial infection and reduces the induction of the antifungal peptide encoding gene Drosomycin after infection by Gram-positive bacteria but not after fungal infection. This phenotype induced by GNBP1 inactivation is identical to a loss-of-function mutation in PGRP-SA, and our genetic studies suggest that GNBP1 acts upstream of the Toll ligand Spätzle. Altogether, our results demonstrate that the detection of Gram-positive bacteria in Drosophila requires two putative pattern recognition receptors, PGRP-SA and GNBP1.
Volume 279(13)
Pages 12848-53
Published 2004-3-26
DOI 10.1074/jbc.M313324200
PII M313324200
PMID 14722090
MeSH Animals Carrier Proteins / chemistry Carrier Proteins / genetics* Carrier Proteins / physiology* Drosophila / microbiology* Drosophila Proteins / chemistry Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila Proteins / physiology* Gene Silencing Genetic Predisposition to Disease* Gram-Positive Bacterial Infections / prevention & control* Peptides / chemistry Phenotype RNA Interference* RNA, Double-Stranded / biosynthesis Receptors, Cell Surface / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors Toll-Like Receptors
IF 4.106
Times Cited 104
Drosophila 6895R-1 6895R-2