Chopping GSDMD : caspase‐8 has joined the team of pyroptosis‐mediating caspases

Inflammatory and apoptotic caspases mediate two distinct forms of cell death: pyroptosis and apoptosis, respectively. Three independent studies have now demonstrated that the “apoptotic” caspase‐8 can cleave gasdermin D ( GSDMD ) leading to pyroptosis‐like cell death and IL ‐1β release in murine macrophages (Orning et al , 2018; Sarhan et al , 2018; Chen et al , 2019). Orning et al and Chen/Demarco et al also show that the NLRP 3 inflammasome is activated downstream of active caspase‐8, but they attribute this inflammasome activation to different pore‐forming proteins, GSDMD and pannexin‐1, respectively (Orning et al , 2018; Chen et al , 2019).