Recent Insights on Inflammasomes, Gasdermin Pores, and Pyroptosis.

Abstract

Inflammasomes assemble in the cytosol of myeloid and epithelial cells on sensing of cellular stress and pathogen-associated molecular patterns and serve as scaffolds for recruitment and activation of inflammatory caspases. Inflammasomes play beneficial roles in host and immune responses against diverse pathogens but may also promote inflammatory tissue damage if uncontrolled. Gasdermin D (GSDMD) is a recently identified substrate of murine caspase-1 and caspase-11, and human caspases-1, -4, and -5 that mediates a regulated lytic cell death mode termed pyroptosis. Recent studies have identified pyroptosis as a critical inflammasome effector mechanism that controls inflammasome-dependent cytokine secretion and contributes to antimicrobial defense and inflammasome-mediated autoinflammatory diseases. Here, we review recent developments on inflammasome-associated effector functions with an emphasis on the emerging roles of gasdermin pores and pyroptosis.