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ROLE OF NOD1 AND NOD2 IN THE AUTOPHAGIC RESPONSE AGAINST INTRACELLULAR BACTERIA
LH Travassos1, LA Carneiro2, L Yuan1, JG Magalhães1, L Le Bourhis1, I Tatolli2, K Geddes1, S E Girardin2, DJ Philpott1
1Department of Immunology, and 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario
Autophagy is a degradation pathway that plays a major role in keeping cells free of long-lived proteins and organelles. During the induction of autophagy parts of the cytoplasm are engulfed by double- or multiple-membrane structures called autophagosomes. After their complete formation, the autophagosomes fuse with lysosomes and the content is degraded by lysosomal proteases. In the past few years, several studies have highlighted a new protective role for autophagy in the clearance of intracellular bacteria that reach the cytosol, but how they are specifically targeted by autophagy is not clear. Nod2 (and possibly Nod1) are two susceptibility genes for instestinal bowel disease (IBD) that are involved in intracellular bacterial detection. Here, we investigated the putative role of Nod1 and Nod2 in the autophagic response triggered by intracellular bacteria. Through the analysis of the cellular distribution of the autophagy marker GFP-LC3 by fluorescence microscopy and the convertion of LC3-I to LC3-II by western blotting, we present evidence that while Nod1 and Nod2 are not required for starvation- and rapamycin-induced autophagy, Nod1-deficient mouse embryonic fibroblasts display a decreased autophagic response upon infection with Shigella flexneri. In addition, we also observed that in Nod1-deficient cells the number of bacteria present in autophagosomes is significantly reduced in comparison with wild-type cells. Our results identify, for the first time, a link between intracellular detection of bacteria by Nod-like receptors and the induction of autophagy.