FIGURE 1.

Pro‐inflammatory caspases‐triggered pyroptosis. Gasdermin D (GSDMD)‐mediated pyroptosis can be triggered by pro‐inflammatory caspases downstream of canonical or noncanonical inflammasomes. The canonical inflammasome sensors, including NLR family pyrin domain‐containing 1 (NLRP1), NLR family CARD domain containing 4 (NLRC4), caspase recruitment domain‐containing protein 8 (CARD8), NOD‐like receptor protein 3 (NLRP3), absent in melanoma 2 (AIM2) and pyrin, detect diverse stimuli and activate caspase‐1 to cleave GSDMD. IFN‐γ or cytosolic LPS responder guanylate‐binding proteins (GBPs), which are key regulators for noncanonical inflammasome activation, serve as a platform for caspase‐4,5 (or caspase‐11 in mice) recruitment and subsequently cleave GSDMD. Once cleaved, GSDMD^NT fragment can insert into the lipid bilayer of the plasma membrane and subsequently oligomerize to form ring‐like membrane‐spanning pores by regulator‐rag‐mTORC1‐mitochondrial reactive oxygen species (ROS) pathway. ASC, apoptosis‐associated speck‐like protein containing a CARD; DPP, dipeptidyl‐peptidase; GSDMD^NT, the N‐terminal of GSDMD protein; IL‐1β, interleukin‐1β; LPS, lipopolysaccharide; mTORC1, the mechanistic target of rapamycin complex 1