Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, United States.
Biology Department, University of Arkansas at Little Rock, Little Rock, AR 72204, United States.
Microbiol Res. 2023 Jul;272:127383. doi: 10.1016/j.micres.2023.127383. Epub 2023 Apr 10.
The recognition of pathogen- or damage- associated molecular patterns (PAMPs/DAMPs) signals a series of coordinated responses as part of innate immunity or host cell defense during infection. The inflammasome is an assemblage of multiprotein complexes in the cytosol that activate inflammatory caspases and release pro-inflammatory mediators. This review examines the two-edged sword activity of gasdermin D (GSDMD). Since its discovery in 2015, GSDMD has played a crucial role in the programmed necrotic type of cell death called pyroptosis. Pyroptosis is an important response in host self-protection against danger signals and infection. Although excessive pyroptosis has a deleterious effect on the host, it proves to have a game-changing therapeutic application against pathogenic invasion when controlled. Here, we explore the mechanism utilized by GSDMD, the best studied member of the gasdermin protein family, in host immune defense against many bacteria. While the protein contributes to the clearance of some bacteria, we also discussed results from previous studies and research, that its presence might hinder effective immunity against other pathogens, thus aiding pathogenic invasion and spread.
病原体或损伤相关分子模式 (PAMPs/DAMPs) 的识别信号是感染过程中固有免疫或宿主细胞防御的一系列协调反应的一部分。炎症小体是细胞质中多蛋白复合物的集合,可激活炎症半胱天冬酶并释放促炎介质。这篇综述考察了 Gasdermin D (GSDMD) 的双刃剑活性。自 2015 年发现以来,GSDMD 在称为细胞焦亡的程序性坏死性细胞死亡中发挥了关键作用。细胞焦亡是宿主针对危险信号和感染的自我保护的重要反应。尽管过度的细胞焦亡对宿主有有害影响,但当受到控制时,它被证明在对抗病原入侵方面具有改变游戏规则的治疗应用。在这里,我们探讨了 GSDMD(gasdermin 蛋白家族中研究最多的成员)在宿主免疫防御多种细菌中的作用机制。虽然该蛋白有助于清除一些细菌,但我们还讨论了之前研究和研究的结果,表明其存在可能会阻碍对其他病原体的有效免疫,从而有助于病原体的入侵和传播。