The innate immune system senses and responds to pathogens and endogenous damage through supramolecular protein complexes known as inflammasomes. Cytosolic inflammasome sensor proteins trigger inflammasome assembly on detection of infection and danger. Assembled inflammasomes activate a cascade of inflammatory caspases, which process procytokines and gasdermin D (GSDMD). Cleaved GSDMD forms membrane pores that lead to cytokine release and/or programmed lytic cell death, called pyroptosis. In this review, we provide a primer on pyroptosis and focus on its executioner, the GSDM protein family. In addition to inflammasome-mediated GSDMD pore formation, we describe recently discovered GSDMD activation by caspase-8 and elastase in Yersinia-infected macrophages and aging neutrophils, respectively, and GSDME activation by apoptotic caspases. Finally, we discuss strategies that host cells and pathogens use to restrict GSDMD pore formation, in addition to therapeutics targeting the GSDM family.

中文翻译：

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Gasdermin 介导的细胞死亡的机制和调控。

先天免疫系统通过称为炎性体的超分子蛋白复合物感知并响应病原体和内源性损伤。细胞溶质炎性体传感器蛋白在检测到感染和危险时触发炎性体组装。组装的炎性体激活一系列炎性半胱天冬酶，这些半胱天冬酶处理原细胞因子和gasdermin D (GSDMD)。裂解的 GSDMD 形成膜孔，导致细胞因子释放和/或程序性裂解细胞死亡，称为细胞焦亡。在这篇综述中，我们提供了关于细胞焦亡的入门知识，并重点介绍了它的刽子手 GSDM 蛋白家族。除了炎性体介导的 GSDMD 孔形成之外，我们还描述了最近在耶尔森氏菌感染的巨噬细胞和老化的中性粒细胞中分别通过 caspase-8 和弹性蛋白酶激活 GSDMD，以及通过凋亡半胱天冬酶激活 GSDME。最后，