Converging roles of caspases in inflammasome activation, cell death and innate immunity

Accumulating data are highlighting new roles for the caspase family of cysteine proteases beyond their well-established functions in apoptosis and inflammation. This Review describes these emerging roles for caspases in mediating distinct forms of programmed cell death and directing inflammasome and innate immune responses. Inflammatory and apoptotic caspases are central players in inflammation and apoptosis, respectively. However, recent studies have revealed that these caspases have functions beyond their established roles. In addition to mediating cleavage of the inflammasome-associated cytokines interleukin-1β (IL-1β) and IL-18, inflammatory caspases modulate distinct forms of programmed cell death and coordinate cell-autonomous immunity and other fundamental cellular processes. Certain apoptotic caspases assemble structurally diverse and dynamic complexes that direct inflammasome and interferon responses to fine-tune inflammation. In this Review, we discuss the expanding and interconnected roles of caspases that highlight new aspects of this family of cysteine proteases in innate immunity.