Autophagy and inflammasome interplay.

Abstract

Inflammation is a defensive response of the organism to manage harmful stimuli sensed by innate immune cells. The signal alarm is triggered by the recognition of pathogen-associated molecular patterns, such as microbial components, or host-derived damage-associated molecular patterns (DAMPs), namely high-mobility group box 1 protein (HMGB1) and purine metabolites, through a set of highly conserved receptors in immune cells termed pattern recognition receptors. Among these receptors, membrane-associated toll-like receptors (TLRs) and cytosolic nucleotide binding and oligomerization domain (nod)-like receptors (NLRs) assume particular relevance in the inflammatory process. Once activated, NLRs induce the assembly of multiprotein complexes called inflammasomes, leading to production of proinflammatory cytokines (e.g., interleukin-1) and induction of inflammatory cell death (pyroptosis) through the activation of caspase-1. Although these processes intend to protect the body from insults, prolonged or exacerbated inflammatory responses associated with inflammasome activation are related to a growing number of diseases. Recently, inflammasome activation and autophagy were shown to be linked and to mutually influence each other. Therefore, we aim, in this review, to discuss the recent evidences concerning the cross talk between autophagy and inflammasome activation and its potential roles in disease progression.