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

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.