Activation and Regulation of the NLRP3 Inflammasome

Abstract

Inflammation is an immune response to infectious agents and to signals that arise from host molecules in stress situations or after tissue damage. Many innate immune receptors take part in the inflammatory response and induce transcriptional responses leading to the production of a host of cytokines, chemokines, and other inflammatory mediators. The IL-1β cytokines are exceptional in that they not only require transcriptional induction but also proteolytic processing into biologically active cytokines. This proteolytic activation step is mediated by caspase-1, which itself is controlled by cytosolic multimolecular complexes that are termed inflammasomes. The NLRP3 inflammasome responds to aggregated or crystalline material, microbes or pore-forming toxins and the activation mechanisms are not fully understood. The importance of this innate signaling complex is highlighted by the existence of several mechanisms that regulate NLRP3 activation at different levels.