Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 38 Dengzhou Road, Qingdao 266021, China.
Int J Biol Sci. 2022 Sep 21;18(15):5827-5848. doi: 10.7150/ijbs.77561. eCollection 2022.
The rapid dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), remains a global public health emergency. The host immune response to SARS-CoV-2 plays a key role in COVID-19 pathogenesis. SARS-CoV-2 can induce aberrant and excessive immune responses, leading to cytokine storm syndrome, autoimmunity, lymphopenia, neutrophilia and dysfunction of monocytes and macrophages. Pyroptosis, a proinflammatory form of programmed cell death, acts as a host defense mechanism against infections. Pyroptosis deprives the replicative niche of SARS-CoV-2 by inducing the lysis of infected cells and exposing the virus to extracellular immune attack. Notably, SARS-CoV-2 has evolved sophisticated mechanisms to hijack this cell death mode for its own survival, propagation and shedding. SARS-CoV-2-encoded viral products act to modulate various key components in the pyroptosis pathways, including inflammasomes, caspases and gasdermins. SARS-CoV-2-induced pyroptosis contriubtes to the development of COVID-19-associated immunopathologies through leakage of intracellular contents, disruption of immune system homeostasis or exacerbation of inflammation. Therefore, pyroptosis has emerged as an important mechanism involved in COVID-19 immunopathogenesis. However, the entangled links between pyroptosis and SARS-CoV-2 pathogenesis lack systematic clarification. In this review, we briefly summarize the characteristics of SARS-CoV-2 and COVID-19-related immunopathologies. Moreover, we present an overview of the interplay between SARS-CoV-2 infection and pyroptosis and highlight recent research advances in the understanding of the mechanisms responsible for the implication of the pyroptosis pathways in COVID-19 pathogenesis, which will provide informative inspirations and new directions for further investigation and clinical practice. Finally, we discuss the potential value of pyroptosis as a therapeutic target in COVID-19. An in-depth discussion of the underlying mechanisms of COVID-19 pathogenesis will be conducive to the identification of potential therapeutic targets and the exploration of effective treatment measures aimed at conquering SARS-CoV-2-induced COVID-19.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的快速传播仍然是全球公共卫生紧急事件，它是导致 2019 年冠状病毒病（COVID-19）的病原体。宿主对 SARS-CoV-2 的免疫反应在 COVID-19 的发病机制中起着关键作用。SARS-CoV-2 可诱导异常和过度的免疫反应，导致细胞因子风暴综合征、自身免疫、淋巴细胞减少、中性粒细胞增多以及单核细胞和巨噬细胞功能障碍。细胞焦亡是一种炎症性的程序性细胞死亡形式，作为宿主防御感染的机制。细胞焦亡通过诱导感染细胞裂解并使病毒暴露于细胞外免疫攻击，剥夺 SARS-CoV-2 的复制小生境。值得注意的是，SARS-CoV-2 已经进化出复杂的机制来劫持这种细胞死亡模式以促进其自身的存活、繁殖和释放。SARS-CoV-2 编码的病毒产物作用于调节细胞焦亡途径中的各种关键成分，包括炎性小体、半胱天冬酶和 gasdermins。SARS-CoV-2 诱导的细胞焦亡通过细胞内物质的渗漏、免疫系统稳态的破坏或炎症的加剧导致 COVID-19 相关免疫病理学的发展。因此，细胞焦亡已成为 COVID-19 免疫发病机制中的一个重要机制。然而，细胞焦亡与 SARS-CoV-2 发病机制之间错综复杂的联系仍缺乏系统的阐明。在这篇综述中，我们简要总结了 SARS-CoV-2 和 COVID-19 相关免疫病理学的特征。此外，我们概述了 SARS-CoV-2 感染与细胞焦亡之间的相互作用，并强调了对理解细胞焦亡途径在 COVID-19 发病机制中的作用的最新研究进展，这将为进一步研究和临床实践提供有价值的启示和新方向。最后，我们讨论了细胞焦亡作为 COVID-19 治疗靶点的潜在价值。深入探讨 COVID-19 发病机制的潜在机制将有助于确定潜在的治疗靶点，并探索针对征服 SARS-CoV-2 诱导的 COVID-19 的有效治疗措施。
