Inflammasomes and intestinal inflammation

The inflammasome is a cytosolic multi-protein innate immune rheostat, sensing a variety of endogenous and environmental stimuli, and regulating homeostasis or damage control. In the gastrointestinal tract, inflammasomes orchestrate immune tolerance to microbial and potentially food-related signals or drive the initiation of inflammatory responses to invading pathogens. When inadequately regulated, intestinal inflammasome activation leads to a perpetuated inflammatory response leading to immune pathology and tissue damage. In this review, we present the main features of the predominant types of inflammasomes participating in intestinal homeostasis and inflammation. We then discuss current controversies and open questions related to their functions and implications in disease, highlighting how pathological inflammasome over-activation or impaired function impact gut homeostasis, the microbiome ecosystem, and the propensity to develop gut-associated diseases. Collectively, understanding of the molecular basis of intestinal inflammasome signaling may be translated into clinical manipulation of this fundamental pathway as a potential immune modulatory therapeutic intervention.