Figure 1.

The canonical pyroptosis pathway. PAMPs are recognized by PRRs and form inflammasome complexes, in which NLRP3 is the representative. The inflammasome activates and cleaves pro-caspase-1 into caspase-1 through the adaptor protein ASC, which cleaves GSDMD into an N-terminal domain (GSDMD-N) with perforating activity. GSDMD-N forms non-selective oligomeric pores in the plasma membrane through membrane-lipid interactions. The cells died because of water influx, swelling and rupture. In addition, caspase-1 can also activate inflammatory cytokines like IL-1β and IL-18 which are released into the extracellular fluid via membrane pores and exacerbate the inflammatory response.