Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
Harvard Medical School & Boston Children's Hospital, Boston, MA, USA.
Nat Rev Mol Cell Biol. 2022 Apr;23(4):286-301. doi: 10.1038/s41580-021-00430-1. Epub 2021 Nov 23.
Double-stranded RNA (dsRNA) is associated with most viral infections - it either constitutes the viral genome (in the case of dsRNA viruses) or is generated in host cells during viral replication. Hence, nearly all organisms have the capability of recognizing dsRNA and mounting a response, the primary aim of which is to mitigate the potential infection. In vertebrates, a set of innate immune receptors for dsRNA induce a multitude of cell-intrinsic and cell-extrinsic immune responses upon dsRNA recognition. Notably, recent studies showed that vertebrate cells can accumulate self-derived dsRNAs or dsRNA-like species upon dysregulation of several cellular processes, activating the very same immune pathways as in infected cells. On the one hand, such aberrant immune activation in the absence of infection can lead to pathogenesis of immune disorders, such as Aicardi-Goutières syndrome. On the other hand, the same innate immune reaction can be induced in a controlled setting for a therapeutic benefit, as occurs in immunotherapies. In this Review, we describe mechanisms by which immunostimulatory dsRNAs are generated in mammalian cells, either by viruses or by the host cells, and how cells respond to them, with the focus on recent developments regarding the role of cellular dsRNAs in immune modulation.
双链 RNA（dsRNA）与大多数病毒感染有关 - 它要么构成病毒基因组（双链 RNA 病毒的情况），要么在病毒复制过程中在宿主细胞中产生。因此，几乎所有生物体都具有识别 dsRNA 并做出反应的能力，其主要目的是减轻潜在感染的风险。在脊椎动物中，一组针对 dsRNA 的先天免疫受体在识别 dsRNA 后会诱导多种细胞内和细胞外免疫反应。值得注意的是，最近的研究表明，脊椎动物细胞在几种细胞过程失调时可以积累自身衍生的 dsRNA 或 dsRNA 样物质，从而激活与感染细胞中相同的免疫途径。一方面，在没有感染的情况下这种异常的免疫激活可能导致免疫紊乱等疾病的发病机制，如 Aicardi-Goutières 综合征。另一方面，相同的先天免疫反应可以在受控环境中诱导以获得治疗益处，如免疫疗法中那样。在这篇综述中，我们描述了免疫刺激性 dsRNA 在哺乳动物细胞中产生的机制，无论是由病毒还是宿主细胞产生的，以及细胞如何对其做出反应，重点介绍了关于细胞内 dsRNA 在免疫调节中的作用的最新进展。
