Increasing complexity of NLRP3 inflammasome regulation.

Inflammasomes are multiprotein complexes that assemble upon detection of danger signals to activate the inflammatory enzyme caspase-1, trigger secretion of the highly proinflammatory cytokine IL-1β, and induce an inflammatory cell death called pyroptosis. Distinctiveness of the nucleotide-binding oligomerization (NOD), Leucine-rich repeat (LRR)-containing protein (NLRP3) inflammasome resides in the diversity of molecules that induce its activation, indicating a certain intricacy. Furthermore, besides the canonical activation of NLRP3 in response to various stimuli, caspase-11-dependent detection of intracellular LPS activates NLRP3 through a noncanonical pathway. Several aspects of the NLRP3 inflammasome are not characterized or remain unclear. In this review, we summarize the different modes of NLRP3 activation. We describe recent insights into post-translational and cellular regulation that confer further complexity to NLRP3 inflammasomes. ©2020 Society for Leukocyte Biology.