Figure 1

Canonical and noncanonical inflammasomes. A typical inflammasome contains a sensor protein belonging to either the NLR or ALR family of pattern recognition receptors, an adaptor protein ASC and pro-caspase-1. NAIP-NLRC4 is activated by bacterial flagellin and type III secretion system proteins, NLRP1 is activated by lethal toxin and muramyl dipeptide, AIM2 is activated by cytosolic dsDNA and NLRP3 is activated by a variety of activators including ATP, uric acid, alum, β-amyloid, MSU and nigericin. Activation of these inflammasome complexes results in proteolytic cleavage of zymogen pro-caspase-1 into its enzymatically active form, which then leads to maturation of proinflammatory cytokines IL-1β and IL-18. In the noncanonical inflammasome pathway, pro-caspase-11 expression is induced by a variety of Toll-like receptor ligands, or via type I interferon signaling. Caspase-11 is self-oligomerized and activated by cytosolic LPS, which subsequently leads to caspase-1 activation, as well as gasdermin D-mediated pyroptotic cell death in macrophages.