Caspases and immunity in a deadly grip

Caspases are crucial for the execution of apoptotic cell death. However, caspase-1, the first identified mammalian caspase, was not discovered in the context of apoptosis, but rather as an enzyme that processes the proinflammatory cytokine interleukin (IL)-1². More recently, additional nonapoptotic roles of apoptotic caspases have been uncovered. For example, caspase-8 can counteract necroptosis, an inflammatory mode of cell death induced by receptor-interacting protein (RIP)3. Here, we explore how caspases and their associated proteins and substrates mediate multiple cellular immune processes that extend beyond cell death. We focus on caspases-1, -8 and -11 because of the growing excitement in considering these caspases through the lens of regulators of immunity rather than primarily as arbiters of cell fate.