Robert W. Woodruff Professor Emeritus, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
Professor Emeritus, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Curr Top Microbiol Immunol. 2023;442:1-40. doi: 10.1007/82_2023_264.
Host control over infectious disease relies on the ability of cells in multicellular organisms to detect and defend against pathogens to prevent disease. Evolution affords mammals with a wide variety of independent immune mechanisms to control or eliminate invading infectious agents. Many pathogens acquire functions to deflect these immune mechanisms and promote infection. Following successful invasion of a host, cell autonomous signaling pathways drive the production of inflammatory cytokines, deployment of restriction factors and induction of cell death. Combined, these innate immune mechanisms attract dendritic cells, neutrophils and macrophages as well as innate lymphoid cells such as natural killer cells that all help control infection. Eventually, the development of adaptive pathogen-specific immunity clears infection and provides immune memory of the encounter. For obligate intracellular pathogens such as viruses, diverse cell death pathways make a pivotal contribution to early control by eliminating host cells before progeny are produced. Pro-apoptotic caspase-8 activity (along with caspase-10 in humans) executes extrinsic apoptosis, a nonlytic form of cell death triggered by TNF family death receptors (DRs). Over the past two decades, alternate extrinsic apoptosis and necroptosis outcomes have been described. Programmed necrosis, or necroptosis, occurs when receptor interacting protein kinase 3 (RIPK3) activates mixed lineage kinase-like (MLKL), causing cell leakage. Thus, activation of DRs, toll-like receptors (TLRs) or pathogen sensor Z-nucleic acid binding protein 1 (ZBP1) initiates apoptosis as well as necroptosis if not blocked by virus-encoded inhibitors. Mammalian cell death pathways are blocked by herpesvirus- and poxvirus-encoded cell death suppressors. Growing evidence has revealed the importance of Z-nucleic acid sensor, ZBP1, in the cell autonomous recognition of both DNA and RNA virus infection. This volume will explore the detente between viruses and cells to manage death machinery and avoid elimination to support dissemination within the host animal.
宿主对传染病的控制依赖于多细胞生物中细胞检测和防御病原体的能力，以防止疾病发生。进化赋予了哺乳动物多种独立的免疫机制来控制或消除入侵的传染性病原体。许多病原体获得了逃避这些免疫机制并促进感染的功能。在成功入侵宿主后，细胞自主信号通路会驱动炎症细胞因子的产生、限制因子的部署和细胞死亡的诱导。这些先天免疫机制共同吸引树突状细胞、中性粒细胞和巨噬细胞以及自然杀伤细胞等先天淋巴细胞，共同帮助控制感染。最终，适应性的病原体特异性免疫的发展清除了感染，并提供了对该遭遇的免疫记忆。对于病毒等必需的细胞内病原体，多种细胞死亡途径通过在产生后代之前消除宿主细胞，对早期控制做出了至关重要的贡献。促凋亡半胱天冬酶-8 活性（人类中还有半胱天冬酶-10）执行外在凋亡，这是一种由 TNF 家族死亡受体（DR）触发的非溶细胞形式的细胞死亡。在过去的二十年中，已经描述了替代的外在凋亡和坏死性凋亡结果。程序性坏死或坏死性凋亡发生在受体相互作用蛋白激酶 3（RIPK3）激活混合谱系激酶样（MLKL）时，导致细胞渗漏。因此，如果不被病毒编码的抑制剂阻断，DR、 Toll 样受体（TLR）或病原体传感器 Z 核酸结合蛋白 1（ZBP1）的激活会引发凋亡和坏死性凋亡。疱疹病毒和痘病毒编码的细胞死亡抑制剂阻断了哺乳动物的细胞死亡途径。越来越多的证据表明，Z 核酸传感器 ZBP1 在细胞自主识别 DNA 和 RNA 病毒感染方面具有重要作用。本卷将探讨病毒和细胞之间的平衡，以管理死亡机制并避免消除，以支持在宿主动物体内的传播。
