Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Shenzhen Bay Laboratory, Institute of Infectious Diseases, Shenzhen, 518000, China.
Cell Death Dis. 2022 Jul 22;13(7):637. doi: 10.1038/s41419-022-05066-3.
Since the discovery of cell apoptosis, other gene-regulated cell deaths are gradually appreciated, including pyroptosis, ferroptosis, and necroptosis. Necroptosis is, so far, one of the best-characterized regulated necrosis. In response to diverse stimuli (death receptor or toll-like receptor stimulation, pathogenic infection, or other factors), necroptosis is initiated and precisely regulated by the receptor-interacting protein kinase 3 (RIPK3) with the involvement of its partners (RIPK1, TRIF, DAI, or others), ultimately leading to the activation of its downstream substrate, mixed lineage kinase domain-like (MLKL). Necroptosis plays a significant role in the host's defense against pathogenic infections. Although much has been recognized regarding modulatory mechanisms of necroptosis during pathogenic infection, the exact role of necroptosis at different stages of infectious diseases is still being unveiled, e.g., how and when pathogens utilize or evade necroptosis to facilitate their invasion and how hosts manipulate necroptosis to counteract these detrimental effects brought by pathogenic infections and further eliminate the encroaching pathogens. In this review, we summarize and discuss the recent progress in the role of necroptosis during a series of viral, bacterial, and parasitic infections with zoonotic potentials, aiming to provide references and directions for the prevention and control of infectious diseases of both human and animals.
自细胞凋亡被发现以来，人们逐渐认识到其他受基因调控的细胞死亡方式，包括细胞焦亡、铁死亡和坏死性凋亡。坏死性凋亡是迄今为止研究最为充分的一种受调控的细胞坏死方式。在受到多种刺激（死亡受体或 Toll 样受体刺激、病原体感染或其他因素）后，坏死性凋亡由受体相互作用蛋白激酶 3（RIPK3）起始并受到其伴侣（RIPK1、TRIF、DAI 或其他蛋白）的精确调控，最终导致其下游底物混合谱系激酶结构域样蛋白（MLKL）的激活。坏死性凋亡在宿主抵御病原体感染中发挥着重要作用。尽管人们已经认识到在病原体感染过程中坏死性凋亡的调节机制，但坏死性凋亡在传染性疾病的不同阶段的确切作用仍在不断揭示中，例如病原体如何以及何时利用或逃避坏死性凋亡以促进其入侵，以及宿主如何操纵坏死性凋亡来对抗这些由病原体感染引起的有害影响并进一步清除入侵的病原体。在这篇综述中，我们总结和讨论了坏死性凋亡在一系列具有动物源性的病毒、细菌和寄生虫感染中的作用的最新进展，旨在为人类和动物传染病的预防和控制提供参考和指导。
