The NLRP3 inflammasome: a sensor of immune danger signals

Abstract

The innate immune system senses danger signals via evolutionary conserved receptors. The nucleotide-binding domain leucine-rich repeat containing receptor (NLR) family is a group of intracellular receptors that drive a wide variety of inflammatory responses. A number of the NLR family members can form inflammasomes, which are multiprotein complexes that can activate caspase-1 and ultimately lead to the processing and secretion of interleukin (IL)-1beta, IL-18 and IL-33. One of the best-studied members of the NLR family is NLRP3 for which a number of divergent activators have recently been described. These and other studies examining the NLRP3 inflammasome will be discussed in this review.

Figure 1

Model of NLRP3 inflammasome activation. Endogenous and exogenous danger signals engage various cytosolic events towards the assembly of a multiprotein complex composed of the cytosolic nucleotide-binding domain leucine-rich repeat containing receptor NLRP3, the adaptor molecule ASC and the cysteine protease caspase-1. Once activated, the NLRP3 inflammasome results in caspase-1 activation leading to the processing and secretion of the proinflammatory cytokines IL-1β, IL-18 and IL-33. The commonality between signals involved in pathways as distinct as cell surface mediated events and lysosomal disruption is yet to be discovered, however, a unique molecule at the crossroads of these pathways is likely involved.