Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae

Abstract

In Drosophila, microbial infection activates an antimicrobial defense system involving the activation of proteolytic cascades in the hemolymph and intracellular signaling pathways, the immune deficiency (imd) and Toll pathways, in immune-responsive tissues. The mechanisms for microbial recognition are largely unknown. We report that, in larvae, the imd-mediated antibacterial defense is activated by peptidoglycan-recognition protein (PGRP)-LE, a PGRP-family member in Drosophila. Consistent with this, PGRP-LE binds to the diaminopimelic acid-type peptidoglycan, a cell-wall component of the bacteria capable of activating the imd pathway, but not to the lysine-type peptidoglycan. Moreover, PGRP-LE activates the prophenoloxidase cascade, a proteolytic cascade in the hemolymph. Therefore, PGRP-LE acts as a pattern-recognition receptor to the diaminopimelic acid-type peptidoglycan and activates both the proteolytic cascade and intracellular signaling in Drosophila immunity.

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella

“…Insect PGRPs have been shown to play an important role in detecting pathogens and activating NF-jB through the Toll and Imd pathways (Takehana et al, 2002;Gobert et al, 2003;Silverman et al, 2009). In vertebrates, PRRs such as TLRs and NODs were shown to participate in the signaling pathway leading to NF-jB activation (Shi et al, 2008;Hasegawa et al, 2008), whereas the link between PGRPs and NF-jB is still ambiguous.…”

“…Insect PGRPs are expressed mainly in immune competent sites such as fat body, gut and haemocytes (Werner et al, 2000). The activation of insect PGRPs by Gram-positive or Gram-negative bacteria may trigger Toll (Gobert et al, 2003) and immune deficiency (Imd) signal transduction pathways (Takehana et al, 2002) and the prophenol-oxidase cascade (Takehana et al, 2002), which results in the production of antimicrobial effectors. In addition, some insect PGRPs such as Drosophila PGRP-SC1 and PGRP-LB are N-acetylmuramoyl-L-alanine amidases (Kim et al, 2003;Mellroth et al, 2003), which can hydrolyze proinflammatory peptidoglycans.…”

Methods to study Drosophila immunity

“…2A) and many mutations are done in the y,w background which shows higher immunoreactivity than for example ore R or Can S . The best way to activate the Imd pathway is to over-express Imd, PGRP-LC, PGRP-LE or the truncated, transcriptionally active form of Relish (Rel68) [44][45][46][47].…”

Induction of autophagy via innate bacterial recognition

“…PGRP-LE, first reported by our group to be an extracellular bacteria recognition protein, exists in both the hemolymph and inside hemocytes, the immune reactive cells, and can activate immune signaling in response to a bacterial component inside cultured cells. [13][14][15] These findings led us to examine the function of PGRP-LE as a recognition receptor for intracellular bacteria, and to further study PGRP-LE mediated innate immune responses against intracellular bacteria.…”