Nod1 deficiency inhibits autophagy against Salmonella typhimurium in macrophages (136.21)

Abstract

Abstract Autophagy is a conserved bulk-degradation process involving double-membraned structures called autophagosomes that degrade damaged organelles. Recently, it has been reported that autophagy is important in immunity to microbial pathogens whereby intracellular bacteria are targeted for clearance by autophagy. However, the exact mechanism of how these microbes are identified by autophagy within host cells is still not clear. Innate immune cells rely on pathogen recognition receptors such as nucleotide-binding oligomerization-domain (NOD) like receptor (NLR) family to mount an appropriate immune response against pathogens. The NLR proteins Nod1 and Nod2 were shown to be important for bacterial clearance in dendritic cells. In this context, we found that Nod1 regulates autophagy in macrophages infected with Salmonella typhimurium . Infection of wild-type bone marrow-derived macrophages with Salmonella increased LC3-I lipidation to LC3-II as observed by Western blot. However, Nod1 deficient macrophages showed reduced LC3-II expression and thus autophagy. There were fewer cells with LC3-GFP autophagomes in macrophages deficient for Nod1 as compared to infected wild-type macrophages. Activation of Nod1 and Nod2 initiates a pro-inflammatory response by NF-kB pathway through the recruitment of adaptor protein RICK. We found a similar result in RICK deficient macrophages infected with Salmonella . Our results show a potential role for Nod1 in antibacterial autophagy activation.