Inflammatory Caspases: Linking an Intracellular Innate Immune System to Autoinflammatory Diseases

Caspases not only play an essential role during apoptotic cell death, but a subfamily of them—the inflammatory caspases—are associated with immune responses to microbial pathogens. Activation of inflammatory caspases, such as caspase-1 and caspase-5, occurs upon assembly of an intracellular complex, designated the inflammasome. This results in the cleavage and activation of the proinflammatory cytokines IL-1(beta) and IL-18. Mutations in one of the scaffold proteins of the inflammasome, NALP3/Cryopyrin, are associated with autoinflammatory disorders underscoring the importance of regulating inflammatory caspase activation.