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. 2023 May 18;14:1178662. doi: 10.3389/fimmu.2023.1178662

Figure 2.

Figure 2

Schematic diagram of the mechanisms of GSDMD activation and pyroptosis. In response to various PAMPs or DAMPs, inflammatory caspase-1/4/5/11 is activated, leading to GSDMD cleavage and activation. In addition, apoptotic caspase-8 activation induced by Yersinia infection cleaves GSDMD into GSDMD-NT. The activated GSDMD-NT oligomerizes and inserts into membranes, forming GSDMD pores that lead to ion fluxes, inflammatory cytokine release, and pyroptosis. NLRP1, NOD-, LRR- and pyrin domain-containing protein 1; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; NLRC4, NOD-like receptor family CARD-containing 4; AIM2, absent in melanoma 2; CARD-8, caspase activation and recruitment domain 8; ASC, apoptosis-associated speck-like protein containing a CARD; LPS, lipopolysaccharide; T. gondii, Toxoplasma gondii; T3SS, type III secretion system; dsDNA, double-stranded DNA; YopJ, Yersinia effector protein, also called YopP in Yersinia enterocolitica; NSA, necrosulfonamide; DSF, disulfiram; DMF, dimethyl fumarate.