Fig. 1

Inflammatory responses caused by caspase-8 activation, or deletion, in innate-immune cells. (Left) Other than inducing apoptosis, when activated through TLR, dectin-1 or death receptor signalling, caspase-8 has been reported to activate IL-1β through either the NLRP3–caspase-1 inflammasome or by direct proteolytic IL-1β processing. RIPK3 and caspase-8 signalling downstream of TLR4 is also required for efficient cytokine production independent of their ability to induce cell death. (Right) When caspase-8 is lost, TLR or TNFR1 ligation can activate RIPK1/RIPK3 to induce cytokine production, drive RIPK3–MLKL-dependent necroptosis (and DAMP release) or activate the NLRP3 inflammasome to generate bioactive IL-1β. IL interleukin, MLKL mixed lineage kinase domain-like, NLRP3 Nod-like receptor 3, RIPK receptor interacting protein kinase, TLR Toll-like receptor, TNFR1 tumour necrosis factor receptor 1