Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation

Maintenance of immune homeostasis is an intricate process wherein inflammasomes play a pivotal role by contributing to innate and adaptive immune responses. Inflammasomes are ensembles of adaptor proteins that can trigger a signal following innate sensing of pathogens or non-pathogens eventuating in the inductions of IL-1β and IL-18. These inflammatory cytokines substantially influence the antigen-presenting cell's costimulatory functions and T helper cell differentiation, contributing to adaptive immunity. As acute and chronic disease conditions may accompany parallel tissue damage, we analyze the critical role of extracellular factors such as cytokines, amyloids, cholesterol crystals, etc., intracellular metabolites, and signaling molecules regulating inflammasome activation/inhibition. We develop an operative framework for inflammasome function and regulation by host cell factors and pathogens. While inflammasomes influence the innate and adaptive immune components' interplay modulating the anti-pathogen adaptive immune response, pathogens may target inflammasome inhibition as a survival strategy. As trapped between health and diseases, inflammasomes serve as promising therapeutic targets and their modus operandi serves as a scientific rationale for devising better therapeutic strategies.