Caspase-8 inactivation drives autophagy-dependent inflammasome activation in myeloid cells.

ABSTRACT: Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd^-/-Ripk3^-/- myeloid cells promoted interleukin-1β (IL-1β) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd^-/-Ripk3^-/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1β/IL-18 production. In contrast, inhibiting GSDMD or autoph

SUBMITTER: Wu YH 

PROVIDER: S-EPMC9651862 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature