The peptidoglycan recognition protein PGRP-LE regulates the Drosophila immune response against the pathogen Photorhabdus.

Photorhabdus bacteria are potent pathogens of insects and humans. To elucidate the infection strategies Photorhabdus employs to subvert the host innate immune response, it is critical to use model organisms that permit the genetic dissection of the dynamics involved in host-pathogen interactions. Here, we employed the fruit fly Drosophila melanogaster to interrogate the role of the immune deficiency (Imd) pathway receptor peptidoglycan recognition protein LE (PGRP-LE) in the regulation of the fly's response to the insect pathogen Photorhabdus luminescens and the insect/human pathogen P. asymbiotica. We show that PGRP-LE is upregulated in response to injection of Photorhabdus bacteria in background control flies, and that loss-of-function PGRP-LE mutant flies are more sensitive specifically to P. luminescens infection and harbor a higher bacterial burden of this species compared to background controls. Also, our results indicate that the absence of functional PGRP-LE alters the transcriptional pathway activity of Imd and Jnk signaling upon infection with P. asymbiotica, while infection with P. luminescens modifies the activity of Jak/Stat signaling. These findings denote the participation of the PGRP-LE receptor in the response of D. melanogaster to Photorhabdus challenge and contribute to a better understanding of pathogen detection and host immune regulation against virulent microbial invaders.

Thioester-containing Proteins in the Drosophila melanogaster Immune Response against the Pathogen Photorhabdus.

The fruit fly Drosophila melanogaster forms a magnificent model for interpreting conserved host innate immune signaling and functional processes in response to microbial assaults. In the broad research field of host-microbe interactions, model hosts are used in conjunction with a variety of pathogenic microorganisms to disentangle host immune system activities and microbial pathogenicity strategies. The pathogen Photorhabdus is considered an established model for analyzing bacterial virulence and symbiosis due to its unique life cycle that extends between two invertebrate hosts: an insect and a parasitic nematode. In recent years, particular focus has been given to the mechanistic participation of the D. melanogaster thioester-containing proteins (TEPs) in the overall immune capacity of the fly upon response against the pathogen Photorhabdus alone or in combination with its specific nematode vector Heterorhabditis bacteriophora. The original role of certain TEPs in the insect innate immune machinery was linked to the antibacterial and antiparasite reaction of the mosquito malaria vector Anopheles gambiae; however, revamped interest in the immune competence of these molecules has recently emerged from the D. melanogaster-Photorhabdus infection system. Here, we review the latest findings on this topic with the expectation that such information will refine our understanding of the evolutionary immune role of TEPs in host immune surveillance.