Abstract
Peptidoglycan-recognition proteins (PGRPs) are evolutionarily conserved molecules that are structurally related to bacterial amidases. Several Drosophila PGRPs have lost this enzymatic activity and serve as microbe sensors through peptidoglycan recognition. Other PGRP family members, such as Drosophila PGRP-SC1 or mammalian PGRP-L, have conserved the amidase function and are able to cleave peptidoglycan in vitro. However, the contribution of these amidase PGRPs to host defense in vivo has remained elusive so far. Using an RNA-interference approach, we addressed the function of two PGRPs with amidase activity in the Drosophila immune response. We observed that PGRP-SC1/2–depleted flies present a specific over-activation of the IMD (immune deficiency) signaling pathway after bacterial challenge. Our data suggest that these proteins act in the larval gut to prevent activation of this pathway following bacterial ingestion. We further show that a strict control of IMD-pathway activation is essential to prevent bacteria-induced developmental defects and larval death.
Highlights
The antimicrobial host defense of Drosophila involves rapid synthesis of small-sized cationic peptides by the fat body [1,2]
In order to address the function of N-acetylmuramyl-L-alanine amidases (NAMLAA) peptidoglycan-recognition protein (PGRP) under in vivo conditions, we analyzed the immune response of Drosophila with reduced PGRP-SC1 and PGRP-SC2 levels
Our data provide novel insights into the physiological roles of PGRPs in Drosophila. They show that in addition to the function as a pattern-recognition receptor of some PGRP family members, others can control the level of activation of the immune deficiency (IMD) signaling pathway
Summary
The antimicrobial host defense of Drosophila involves rapid synthesis of small-sized cationic peptides by the fat body [1,2]. These antimicrobial peptides are released into the open circulatory system where they attack invading microorganisms. The Toll pathway, which is primarily activated after gram-positive bacterial and fungal infections, controls the expression of drosomycin, an antifungal peptide, together with many other genes via the NF-jB–family member DIF (dorsal-related immune factor) [3,4]. The second cascade, known as the IMD (immune deficiency) signaling pathway, is predominantly triggered after gram-negative infection and regulates, via the NF-jB protein Relish, the synthesis of some antibacterial peptides and many other genes [5,6]. On the other hand, sensing of gram-negative bacterial infection has been shown to be dependent on two other PGRP family members, PGRP-LC [11,12,13] and PGRP-LE [14,15]
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