Type I Interferons (IFN-I) are a family of potent antiviral cytokines that act through the direct restriction of viral replication and by enhancing antiviral immunity. However, these powerful cytokines are a caged lion, as excessive and sustained IFN-I production can drive immunopathology during infection, and aberrant IFN-I production is a feature of several types of autoimmunity. As specialized producers of IFN-I plasmacytoid (p), dendritic cells (DCs) can secrete superb quantities and a wide breadth of IFN-I isoforms immediately after infection or stimulation, and are the focus of this review. Notably, a few days after viral infection pDCs tune down their capacity for IFN-I production, producing less cytokines in response to both the ongoing infection and unrelated secondary stimulations. This process, hereby referred to as “pDC exhaustion”, favors viral persistence and associates with reduced innate responses and increased susceptibility to secondary opportunistic infections. On the other hand, pDC exhaustion may be a compromise to avoid IFN-I driven immunopathology. In this review we reflect on the mechanisms that initially induce IFN-I and subsequently silence their production by pDCs during a viral infection. While these processes have been long studied across numerous viral infection models, the 2019 coronavirus disease (COVID-19) pandemic has brought their discussion back to the fore, and so we also discuss emerging results related to pDC-IFN-I production in the context of COVID-19.

中文翻译：

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病毒感染期间 I 型干扰素的诱导和耗尽：浆细胞样树突状细胞和新出现的 COVID-19 研究结果

I 型干扰素 (IFN-I) 是一类强效抗病毒细胞因子，通过直接限制病毒复制和增强抗病毒免疫力发挥作用。然而，这些强大的细胞因子是一头笼中的狮子，因为过量且持续的 IFN-I 产生会在感染期间驱动免疫病理学，并且异常的 IFN-I 产生是几种类型自身免疫的一个特征。作为 IFN-I 类浆细胞 (p) 的专门生产者，树突状细胞 (DC) 在感染或刺激后可以立即分泌大量且广泛的 IFN-I 同工型，也是本综述的重点。值得注意的是，病毒感染几天后，pDC 会降低其产生 IFN-I 的能力，从而响应持续感染和不相关的继发刺激而产生较少的细胞因子。这一过程被称为“pDC耗竭”，有利于病毒持续存在，并与先天反应减少和继发性机会性感染易感性增加相关。另一方面，pDC 耗竭可能是避免 IFN-I 驱动的免疫病理学的折衷方案。在这篇综述中，我们反思了病毒感染期间最初诱导 IFN-I 并随后抑制 pDC 产生 IFN-I 的机制。虽然这些过程已经在多种病毒感染模型中进行了长期研究，但 2019 年冠状病毒病 (COVID-19) 大流行使他们的讨论重新回到了前台，因此我们还讨论了与 pDC-IFN-I 生产相关的新结果COVID-19。