Fig. 1

Inflammasome-dependent pathway of pyroptosis. A Inflammasome sensors are cytosolic proteins that contain a PYD and/or a CARD. They may also contain a LRR, NACHT, HIN-200 domain, B30.2 domain, C–C, B-box domain (B), BIR, or FIIND. Upon detection of specific stimuli, sensors with a PYD recruit adaptor protein ASC to mediate CARD–CARD interactions with the effector cysteine protease caspase-1. Of note, NLRC4 and murine NLRP1b can interact directly with caspase-1 without ASC recruiting them. Nek7 is an important component of the murine NLRP3 inflammasome, binding to the LRR and NACHT of NLRP3. B Canonical pathway: inflammasome sensors can be activated by various signals followed by oligomerization with ASC and pro-caspase-1. Activated caspase-1 cleaves GSDMD to release the N-terminal domain (GSDMD-N), which then induces pyroptosis. Caspase-1 also cleaves pro-IL-1β and pro-IL-18 into their active forms, which are released through GSDMD pores. C Noncanonical pathway: caspase-4/5/11 can be directly activated by LPS, leading to GSDMD cleavage and cell contents and K⁺ release. K⁺ efflux further promotes the activation of caspase-1. PYD pyrin domain, CARD caspase activation and recruitment domain, LRR leucine-rich repeat domain, NACHT nucleotide-binding NACHT domain, C–C coiled–coil domain, BIR baculovirus inhibitor of apoptosis repeat, FIIND function-to-find domain, Nek7 NIMA-related kinase 7, GSDMD gasdermin D, IL interleukin, LPS lipopolysaccharide