RNASeq of Autophagy Mutant BMDMs. RNASeq of Autophagy Mutant BMDMs

Autophagy is an essential cellular process that is deeply integrated with innate immune signaling; however, studies that examine autophagy in the context of inflammatory conditions are lacking. Here, using mouse models with a constitutively active variant of the autophagy gene Beclin1, we show that increased autophagy dampens cytokine production in models of inflammation and adherent-invasive Escherichia coli (AIEC) infection. We further analyzed primary macrophages from these animals with a combination of transcriptomics and proteomics to identify novel mechanistic targets downstream of autophagy. Our study reveals glutamine metabolism and the RNF128/TBK1 axis as independent regulators of inflammation. Altogether, our work highlights increased autophagic flux as a potential approach to reduce inflammation and defines independent mechanistic cascades involved in this control. Overall design: BMDMs differentiated from autophagy mutants and their littermates were harvested at 0,6, and 24 hours post-LPS/IFNgamma stimulation