The Drosophila immune system detects bacteria through specific peptidoglycan recognition

Abstract

The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through 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 infection by Gram-negative bacteria. The bacterial components recognized by these pathways remain to be defined. Here we report that Gram-negative diaminopimelic acid-type peptidoglycan is the most potent inducer of the Imd pathway and that the Toll pathway is predominantly activated by Gram-positive lysine-type peptidoglycan. Thus, the ability of Drosophila to discriminate between Gram-positive and Gram-negative bacteria relies on the recognition of specific forms of peptidoglycan.

Peptidoglycan recognition proteins (PGRPs)

“…Bactericidal effect in PMNs (d) [25], although both types of peptidoglycan bind to PGRP-SA [12]. The probable reason for the weak Toll-activating capacity of DAP-type peptidoglycan is that this peptidoglycan, but not Lys-type peptidoglycan, is the substrate for the carboxypeptidase activity of PGRP-SA [12] (Figure 4d).…”

“…Activation of Drosophila PGRP-LC by Gram-negative bacteria and Gram-positive bacilli (also called rods) triggers another signal transduction pathway, the Imd pathway [19,25,[29][30][31][32][33][34] (Figure 4b). Binding of peptidoglycan to Drosophila PGRP-LC induces its oligomerization and recruitment and activation of the death-domain-containing Imd protein [19].…”

“…PGRP-LC responds primarily to DAP-type peptidoglycan. It is a transmembrane protein and has three alternative splice forms (LC-A, LC-B, and LC-C), which differ in the extracellular PGRP domains; they probably cooperate with each other and have somewhat different recognition specificities [25,29,[32][33][34]. PGRP-LC activates the Imd pathway in cooperation with PGRP-LE [35] and also probably with another, as yet unidentified co-receptor (Figure 4b).…”

Methods to study Drosophila immunity

“…To activate a specific branch of the immune response pure elicitors can be used such as TCT (ligand for the Imd activating receptors PGRP-LE and PGRP-LCx/a), DAP-type peptidoglycan (to activate PGRP-LC and PGRP-LE and to a lesser extent PGRP-SA), Lysine-type peptidoglycan (PGRP-SA), b-glucan (GNBP3), proteases (to activate the psh-Toll pathway). Note that pure LPS has no effect on antimicrobial peptide gene expression but most commercially available LPS preparations (Sigma for example) do show activation of Imd because of trace contaminations by peptidoglycan [37,38]. Pure products can be purchased from InvivoGen or obtained from laboratories specialising in bacterial cell wall biochemistry.…”

Bacterial strategies to overcome insect defences

“…Each of these pathways activates specific nuclear factor (NF)-κB transactivators, which in turn switch on specific programmes of transcription. The ability of D. melanogaster to discriminate between Gram-negative and Gram-positive bacteria is based on the recognition of specific forms of peptidoglycan 51 by different PGRPs 52 . The Toll pathway is mainly activated by Gram-positive bacteria and fungi, and induces the synthesis of several peptides, including the antifungal peptide drosomycin.…”