Inflammasome-associated cell death: Pyroptosis, apoptosis, and physiological implications

• Published in: Microbiology and immunology Vol. 64; no. 4; p. 252
• Main Author: Tsuchiya, Kohsuke
• Format: Journal Article
• Language: English
• Published: Australia 01.04.2020
• Subjects: pyroptosis; apoptosis; gasdermin D; caspase-1; inflammasome
• ISSN: 1348-0421
• DOI: 10.1111/1348-0421.12771

Inflammasomes are innate immune mechanisms that promote inflammation by activating the protease caspase-1. Active caspase-1 induces pyroptosis, a necrotic form of regulated cell death, which facilitates the release of intracellular proinflammatory molecules, including IL-1 family cytokines. Recent studies identified mediators of inflammasome-associated cell death and suggested that inflammasomes induce not only pyroptosis, but also apoptosis. Caspase-1 has the potential to induce pyroptosis and apoptosis in a manner that is dependent on the expression of the pyroptosis mediator gasdermin D. Caspase-1-induced apoptosis is mediated by Bid and caspase-7. Caspase-8 is also activated following the formation of inflammasomes and may induce apoptosis. Because inflammasomes contribute to the pathogenesis of inflammatory disorders and host defenses against microbial pathogens, a more detailed understanding of the mechanisms underlying inflammasome-associated cell death may contribute to the development of novel therapeutic strategies for inflammasome-related diseases. Pyroptosis has been implicated in inflammasome-related diseases, and compounds that inhibit this process have been reported. The molecular mechanisms of inflammasome-associated cell death and its physiological implications are discussed herein.