PMC

The role of gasdermin D in pyroptosis driven by non-canonical and canonical inflammasomes. In the non-canonical inflammasome pathway, LPS released into the cytoplasm by Gram-negative bacteria binds to caspase-4 and -5 in humans and to caspase-11 in mice. These caspases cleave the 53-kDa gasdermin D into a 31-kDa N-terminal and a 22-kDa C-terminal fragment. The N-terminal fragment initiates pyroptosis of the cell and activates the NLRP3 inflammasome to drive caspase-1-dependent maturation of the pro-inflammatory cytokine IL-1β. IL-1β is released from the cell upon membrane rupture. In the canonical inflammasome pathway, activation of the NLRP3, NLRC4, AIM2 or Pyrin inflammasome receptor triggers recruitment of the adaptor protein ASC and caspase-1 into the same inflammasome platform. In this case, caspase-1 cleaves both gasdermin D and pro-IL-1β to initiate pyroptosis and maturation of IL-1β, respectively.