Department of Immunology, Microbiology and Transplantation, Laboratory of Inborn Errors of Immunity, Leuven, Belgium.
Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
Eur J Immunol. 2021 May;51(5):1039-1061. doi: 10.1002/eji.202048793. Epub 2021 Apr 4.
Type I IFNs are so-named because they interfere with viral infection in vertebrate cells. The study of cellular responses to type I IFNs led to the discovery of the JAK-STAT signaling pathway, which also governs the response to other cytokine families. We review here the outcome of viral infections in mice and humans with engineered and inborn deficiencies, respectively, of (i) IFNAR1 or IFNAR2, selectively disrupting responses to type I IFNs, (ii) STAT1, STAT2, and IRF9, also impairing cellular responses to type II (for STAT1) and/or III (for STAT1, STAT2, IRF9) IFNs, and (iii) JAK1 and TYK2, also impairing cellular responses to cytokines other than IFNs. A picture is emerging of greater redundancy of human type I IFNs for protective immunity to viruses in natural conditions than was initially anticipated. Mouse type I IFNs are essential for protection against a broad range of viruses in experimental conditions. These findings suggest that various type I IFN-independent mechanisms of human cell-intrinsic immunity to viruses have yet to be discovered.
I 型干扰素之所以如此命名，是因为它们可以干扰脊椎动物细胞中的病毒感染。对细胞对 I 型干扰素反应的研究导致了 JAK-STAT 信号通路的发现，该通路也控制着对其他细胞因子家族的反应。在这里，我们分别回顾了（i）IFNAR1 或 IFNAR2 基因工程和先天性缺陷、（ii）选择性破坏 I 型干扰素反应的 STAT1、STAT2 和 IRF9、（iii）也破坏 II 型（针对 STAT1）和/或 III 型（针对 STAT1、STAT2、IRF9）干扰素反应的 JAK1 和 TYK2 基因工程和先天性缺陷的小鼠和人类病毒感染的结果。对于自然条件下病毒的保护性免疫，人类 I 型干扰素的冗余性比最初预期的要大，这一观点正在浮现。在实验条件下，小鼠 I 型干扰素对于保护免受广泛的病毒感染是必不可少的。这些发现表明，人类细胞固有抗病毒免疫的各种 I 型干扰素非依赖性机制尚未被发现。
