Fig. 3.

New roles of other gasdermins. Granzyme A can enter target cells through perforin and can hydrolyze gasdermin B, which is upregulated by interferon-γ. The IpaH7.8 effector secreted by Shigella flexneri allows GSDMB to be used for 26 S proteasome degradation to inhibit Granzyme A-mediated, GSDMB-induced pyroptosis. Another gasdermin, granzyme B, can induce the maturation of caspase-3 to cleave GSDME, where the mechanism of cell death changes from apoptosis to pyroptosis. Under hypoxic conditions, PD-L1 interacts with p-Stat3-Y705 to promote the GSDMC-induced triggering of pyroptosis, which is promoted by TNFα and CHX but prevented by Stat3. TNF-α activates caspase-8 to cleave GSDMC, thus avoiding caspase-8 activation and instead activating caspase-3-induced pyroptosis. Activated GAS cysteine protease SpeB cleaves GSDMA by direct proteolysis after the Gln246 site 134 to form GSDMA pores in the host cell membrane, promoting the pyroptosis of infected cells and ultimately resulting in local inflammation and the clearance of pathogens