Inflammasomes in inflammatory bowel disease pathogenesis

Inflammasomes are molecular platforms assembled in response to infection or danger signals, and they regulate the activation of caspase-1 and the maturation of the inflammatory cytokines IL-1β and IL-18. In this review, we will summarize the centrality of Nod-like receptor proteins that assemble inflammasomes and regulate intestinal homeostasis by controlling host defense responses, microbiota composition, intestinal inflammation and tissue damage.

In the intestine, the innate immune system evolved to tolerate commensal microorganisms while maintaining the capacity to trigger host defense responses to invading pathogens. Recent findings suggest that inflammasomes play a critical role in the intricate interplay between the local microbial community and the mucosal immune system by sensing commensal bacteria, regulating microbial ecology, establishing the host defense response that discriminates pathogenic from commensal microbes and preventing the emergence of pathobionts. A model to reconcile the conflicting results in the literature on the role of inflammasomes in experimental colitis will be discussed.

A better understanding of the relationship between inflammasome signaling and the intestinal microbiota might provide insight into the complex interaction of the innate immune system with the intestinal environment, and identify new approaches for the treatment of inflammatory bowel disease and gastrointestinal cancer.