R.I.P. dead bacteria, you will not be attacked

Abstract

The Drosophila immune system distinguishes live -and potentially harmful bacteria -from harmless dead bacteria using a novel splice variant of the receptor PGRP-LC.Distinguishing self from non-self is critical for mounting an appropriate immune response. This historical concept by Janeway 1 was the framework for immune discrimination between host and microorganism. However, it was insufficient to explain the finely-tuned discrimination between harmful vs. non-harmful microorganisms or between infection and colonization.Similarly, it could not explain how the immune system could discriminate between living and dead microorganisms. The fact that the same microbial-associated molecular patterns (MAMPs) are shared among microorganisms regardless of pathogenicity or viability is still an unsolved quandary in innate immunity. In this issue of Nature Immunology a paper by Neyen et al. 2 suggests a resolution of this quandary.The innate immune response is a tightly regulated process that consists of different phases. Firstly, there's recognition of ligands e.g. MAMPs. This is followed by activation of genes involved in host defense (antimicrobial peptides, inflammatory cytokines, chemokines). Finally the response ends with the resolution phase. One of the principles that governs the immune response in all organisms is that once the threat has passed, the immune system must downregulate activation (resolution) to avoid over reaction that can lead to the death of the host 3 . In insects, the Immune Deficiency pathway (IMD) has a principal role in responses toGram negative (Gram -) bacterial infection by activating NF-kB-like genes controlling the expression of antimicrobial peptides among others 4, 5 . In contrast to vertebrates, Drosophila's sensing of Grambacteria does not rely on recognition of lipopolysaccharide (LPS) but rather in the