Autophagic control of listeria through intracellular innate immune recognition in drosophila

Abstract

Autophagy, an evolutionally conserved homeostatic process for catabolizing cytoplasmic components, has been implicated in the elimination of intracellular pathogens during mammalian innate immune responses. However, the mechanisms underlying cytoplasmic infection-induced autophagy, and the role of autophagy in host survival against intracellular pathogens are unknown. Here we report that in drosophila, recognition of diaminopimelic acid-type peptidoglycans by the pattern recognition receptor PGRP-LE is crucial for the induction of autophagy, and that autophagy prevents the intracellular growth of Listeria monocytogenes and promotes host survival against this infection. Autophagy induction occurs independently of the Toll and IMD innate signaling pathways. These findings define a clear pathway leading from the intracellular pattern recognition receptors to the induction of autophagy to host defense.

ATG16L1: A multifunctional susceptibility factor in Crohn disease

“…85 Thus, a strong association between defective autophagy and impaired properties counteracting bacterial infections has been reported by numerous studies. 73,[86][87][88][89] However, a recent study has revealed a protective role of Atg16l1 deficiency against intestinal disease induced by the bacterial pathogen model, Citrobacter rodentium. This immunosuppressive role of ATG16L1 deficiency is dependent on the presence of NOD2 90 and adds to the complexity of the role of ATG16L1 in bacterial clearance.…”

Antimicrobial peptides and cell processes tracking endosymbiont dynamics

“…Autophagy is classically activated in response to organelle damage and nutritional deficiency. This process is also involved in many host -bacterial interactions, notably in the clearance of the intracellular pathogen Listeria monocytogenes in Drosophila [74], and in the regulation of Wolbachia populations in nematodes, crustaceans and insects [75,76]. It also plays a critical role in the elimination of dinoflagellate symbionts in the sea anemone Aiptasia pallida [77,78].…”

Autophagy: for better or for worse

“…At distinct levels, autophagy contributes to both innate and adaptive immunity as a regulator and effector [84]. One autophagy effector function in innate immunity is xenophagy, which refers to the autophagy-dependent elimination of intracellular pathogens, including bacteria (S. pyogenes [85], S. flexneri [86], M. tuberculosis [87], S. typhimurium [88] and L. monocytogenes [89]), parasites (T. gondii [90]) and viruses (Herpes simplex virus [91]). In this way, autophagy restricts pathogen replication and survival, and inhibits pathogen-induced cell death in both plants and mice [92,93].…”