NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Department of Immunology, University of Washington, Seattle, Washington 98109, USA; email:
Annu Rev Immunol. 2021 Apr 26;39:77-101. doi: 10.1146/annurev-immunol-112019-072301. Epub 2021 Jan 13.
Nearly all animal cells contain proteins evolved to trigger the destruction of the cell in which they reside. The activation of these proteins occurs via sequential programs, and much effort has been expended in delineating the molecular mechanisms underlying the resulting processes of programmed cell death (PCD). These efforts have led to the definition of apoptosis as a form of nonimmunogenic PCD that is required for normal development and tissue homeostasis, and of pyroptosis and necroptosis as forms of PCD initiated by pathogen infection that are associated with inflammation and immune activation. While this paradigm has served the field well, numerous recent studies have highlighted cross talk between these programs, challenging the idea that apoptosis, pyroptosis, and necroptosis are linear pathways with defined immunological outputs. Here, we discuss the emerging idea of cell death as a signaling network, considering connections between cell death pathways both as we observe them now and in their evolutionary origins. We also discuss the engagement and subversion of cell death pathways by pathogens, as well as the key immunological outcomes of these processes.
几乎所有的动物细胞都含有经过进化以触发其所在细胞死亡的蛋白质。这些蛋白质的激活是通过连续的程序发生的,人们已经付出了很大的努力来描绘程序性细胞死亡 (PCD) 过程背后的分子机制。这些努力导致了凋亡被定义为一种非免疫原性的 PCD 形式,它是正常发育和组织平衡所必需的,而细胞焦亡和坏死性凋亡则被定义为由病原体感染引发的 PCD 形式,与炎症和免疫激活有关。虽然这一范式很好地服务于该领域,但最近的许多研究强调了这些程序之间的串扰,挑战了凋亡、细胞焦亡和坏死性凋亡是具有明确免疫学输出的线性途径的观点。在这里,我们讨论细胞死亡作为信号网络的新兴概念,考虑了现在观察到的和它们的进化起源的细胞死亡途径之间的联系。我们还讨论了病原体对细胞死亡途径的参与和颠覆,以及这些过程的关键免疫学结果。
Annu Rev Immunol. 2021-4-26
Comput Struct Biotechnol J. 2021-8-3
J Mol Biol. 2022-2-28
Pharmacol Ther. 2022-4
Immunol Rev. 2020-9
Front Cell Infect Microbiol. 2019-11-26
Cell Mol Immunol. 2021-5
Front Pharmacol. 2025-7-3
Nat Rev Mol Cell Biol. 2025-4-9
Proc Natl Acad Sci U S A. 2025-2-25
Front Cell Infect Microbiol. 2020-5-29
Cell. 2020-3-19
Curr Top Microbiol Immunol. 2023
Yale J Biol Med. 2019-12-20