An updated view on the functions of caspases in inflammation and immunity

The binary classification of mammalian caspases as either apoptotic or inflammatory is now obsolete. Emerging data indicate that all mammalian caspases are intricately involved in the regulation of inflammation and immunity. They participate in embryonic and adult tissue homeostasis, control leukocyte differentiation, activation and effector functions, and mediate innate and adaptive immunity signaling. Caspases also promote host resistance by regulating anti-oxidant defense and pathogen clearance through regulation of phagosomal maturation, actin dynamics and phagosome-lysosome fusion. Beyond apoptosis, they regulate inflammatory cell death, eliciting rapid pyroptosis of infected cells, while inhibiting necroptosis-mediated tissue destruction and chronic inflammation. In this review, we describe the cellular and molecular mechanisms underlying non-apoptotic functions of caspases in inflammation and immunity and provide an updated view of their functions as central regulators of tissue homeostasis and host defense.