Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.
Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.
复制标题
恒河猴急性SIV感染时CD4 T细胞通过热凋亡快速丢失
DOI：
10.1128/jvi.00808-22
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发表时间：
2022-09-14
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
在急性HIV-1感染期间，CD 4 T细胞耗竭的潜在机制尚未完全了解。在这里，我们表明，半胱氨酸蛋白酶-1诱导的细胞热凋亡（一种高度炎症性的程序性细胞死亡途径）是导致急性猿猴免疫缺陷病毒（SIV）期间肠道相关淋巴组织（GALT）、脾脏和淋巴结中CD 4 T细胞快速耗尽的主要机制。恒河猴感染。干扰素-γ诱导因子16（一种触发细胞凋亡的宿主DNA传感器）的上调也在组织驻留的CD 4 T细胞中观察到，并与病毒载量和CD 4 T细胞损失相关。相反，caspase-3介导的细胞凋亡和病毒细胞毒性仅占CD 4 T细胞死亡的一小部分。其他程序性细胞死亡机制，包括细胞凋亡诱导的半胱天冬酶非依赖性细胞死亡，坏死性凋亡和自噬，没有显着贡献的CD 4 T细胞耗竭。这些数据支持一种模型，其中半胱天冬酶-1介导的细胞凋亡是导致GALT和淋巴器官中CD 4 T细胞损失和促炎细胞因子释放的主要机制。这些发现有助于我们理解急性SIV感染的发病机制，并对治疗策略的发展具有重要意义。在急性HIV-1感染期间，CD 4 T细胞耗竭的不同机制已经被提出。在这项研究中，我们证明，在早期猴免疫缺陷病毒感染，CD 4 T细胞的耗竭主要是由于焦亡。其他机制也可能以较小的方式促进CD 4 T细胞耗竭。
The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16, a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies. IMPORTANCE Different mechanisms for CD4 T cell depletion during acute HIV-1 infection have been proposed. In this study, we demonstrate that in early simian immunodeficiency virus infection, depletion of CD4 T cells is primarily due to pyroptosis. Other mechanisms may also contribute in a minor way to CD4 T cell depletion.
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DOI：
10.1084/jem.187.7.1113
发表时间：
1998-04-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gandhi RT;Chen BK;Straus SE;Dale JK;Lenardo MJ;Baltimore D
通讯作者：
Baltimore D
影响因子：
15.9
作者：
Espert, Lucile;Denizot, Melanie;Biard-Piechaczyk, Martine
通讯作者：
Biard-Piechaczyk, Martine
影响因子：
5.4
作者：
Lu, Wuxun;Demers, Andrew J.;Li, Qingsheng
通讯作者：
Li, Qingsheng
影响因子：
64.8
作者：
Li, QS;Duan, LJ;Haase, AT
通讯作者：
Haase, AT
影响因子：
64.8
作者：
Cooper, Arik;Garcia, Mayra;Nabel, Gary J.
通讯作者：
Nabel, Gary J.