PD-1 Signaling Promotes Control of Chronic Viral Infection by Restricting Type-I-Interferon-Mediated Tissue Damage.
PD-1 Signaling Promotes Control of Chronic Viral Infection by Restricting Type-I-Interferon-Mediated Tissue Damage.
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PD-1 信号传导通过限制 I 型干扰素介导的组织损伤来促进慢性病毒感染的控制。
DOI：
10.1016/j.celrep.2019.10.092
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Egawa,Takeshi
中科院分区：
文献类型：
--
作者：
Raju,Saravanan;Verbaro,DanielJ;Egawa,Takeshi
免疫反应对于病原体消除是必不可少的，但也会导致组织损伤，导致疾病或死亡。然而，目前尚不清楚宿主免疫系统如何平衡感染控制和免受附带组织损伤的保护。在这里，我们表明PD-1介导的免疫反应限制对于持久控制小鼠慢性LCMV感染至关重要。与慢性期的反应相反，亚急性感染期的PD-1阻断反而导致病毒持续存在。这种效应与淋巴结构的损伤有关，随后降低了适应性免疫应答。此外，这种组织损伤是I型干扰素依赖性的，因为干扰素受体和PD-1途径的顺序阻断可预防免疫病理学并增强感染控制。我们的结论是PD-1介导的抑制需要作为一种免疫调节机制，通过拮抗I型干扰素依赖性免疫病理学对慢性病毒感染的持续反应。
Immune responses are essential for pathogen elimination but also cause tissue damage, leading to disease or death. However, it is unclear how the host immune system balances control of infection and protection from the collateral tissue damage. Here, we show that PD-1-mediated restriction of immune responses is essential for durable control of chronic LCMV infection in mice. In contrast to responses in the chronic phase, PD-1 blockade in the subacute phase of infection paradoxically results in viral persistence. This effect is associated with damage to lymphoid architecture and subsequently decreases adaptive immune responses. Moreover, this tissue damage is type I interferon dependent, as sequential blockade of the interferon receptor and PD-1 pathways prevents immunopathology and enhances control of infection. We conclude that PD-1-mediated suppression is required as an immunoregulatory mechanism for sustained responses to chronic viral infection by antagonizing type-I interferon-dependent immunopathology.