Regulation Where Autophagy Intersects the Inflammasome

SIGNIFICANCE: The autophagy and inflammasome pathways are ancient innate immune mechanisms for controlling invading pathogens that are linked by mutual regulation. In addition to controlling the metabolic homeostasis of the cell through nutrient recycling, the "self-eating" process of autophagy is also responsible for the degradation of damaged organelles, cells, and pathogens to protect the integrity of the organism. As a cytosolic pathogen recognition receptor (PRR) complex, the inflammasome both induces and is induced by autophagy through direct interactions with autophagy proteins or through the effects of secondary molecules, such as mitochondrial reactive oxygen species and mitochondrial DNA. RECENT ADVANCES: While the molecular mechanisms of inflammasome activation and regulation are largely unknown, much of the current knowledge has been established through investigation of the role of autophagy in innate immunity. Likewise, regulatory proteins in the NOD-like receptor family, which includes inflammasome PRRs, are able to stimulate autophagy in response to the presence of a pathogen. CRITICAL ISSUES: Many of the newly uncovered links between autophagy and inflammasomes have raised new questions about the mechanisms controlling inflammasome function, which are highlighted in this review. FUTURE DIRECTIONS: Our basic understanding of the mutual regulation of inflammasomes and autophagy will be essential for designing therapeutics for chronic inflammatory diseases, especially those for which autophagy and inflammasome genes have already been linked.