抗病毒免疫中干扰素与炎症信号通路的交互调控：防御反应与维持稳态

Crosstalk between interferon and inflammatory signaling pathways in the immune responses to viral infections:defense and homeostasis

摘要:

天然免疫是机体通过识别自身或外部危险信号后，为维持体内稳态而逐步建立起来的一系列防御反应，当宿主细胞内的模式识别受体识别胞内病原相关分子模式后激活干扰素(interferon, IFN)、核因子-kappa B (nuclear factor-kappa B, NF-κB)和炎性小体等信号通路。IFNs在天然免疫应答中发挥重要作用，它诱导的抗病毒基因能够通过多种方式抵御病毒的感染，炎症反应则是机体自动的防御反应，能够在病毒感染机体时释放促炎性细胞因子以调控机体的免疫反应，进而发挥抗病毒作用。在病毒感染过程中，IFN信号通路与炎症反应调控网络中的关键分子如NF-κB/RelA、PKR等存在一定的交互作用，此外，IFN信号通路及其产生的细胞因子又影响其他信号通路的活化，进而调控机体的免疫应答以维持自身稳态，它们之间的交互调控失衡将会引起过度炎症反应，导致组织器官的免疫病理损伤，例如SARS-CoV-2感染机体时产生的过度炎症反应。本文综述了机体抗病毒免疫过程中干扰素信号通路与炎症反应之间的交互调控，为研发抗病毒策略提供新思路。

关键词:抗病毒免疫;干扰素;炎性小体;先天性免疫;炎症反应

Abstract:

The innate immunity can be considered as the first-line defense cascades that are gradually built up to maintain the host homeostasis in response to the intrinsic or extrinsic danger signals.The host cells have evolved multiple strategies to antagonize viral infections,and the innate immunity signaling pathways including interferon (IFN),nuclear factor-kappa B (NF-κB),and inflammasome will be activated when the pattern recognition receptors of the host cells sense pathogen-associated molecular patterns.IFNs are crucial to the antiviral immunity as they can induce the expression of IFN-stimulated genes to exert antiviral effects through various pathways.In addition,inflammatory response is an automatic defense response that induces the release of proinflammatory cytokines upon viral infection to regulate immune responses and exert antiviral activities.At the same time,IFN signaling pathway interacts with the inflammatory response regulatory network upon viral infections through some key molecules such as NF-κB/RelA and PKR.Furthermore,the IFN signaling pathway and the downstream cytokines can modulate the activation of other signaling pathways,which in turn regulate the immune response to maintain the homeostasis.An imbalance in the crosstalk can lead to excessive inflammatory responses,resulting in tissue injury.For example,the excessive inflammatory response induced by SARS-CoV-2 infection proves to cause tissue injury.In this review,we summarized the crosstalk between the IFN signaling pathway and the inflammatory responses upon viral infections,which was expected to provide insights into the future research on antiviral strategies.

Key words:antiviral immunity;interferon;inflammasome;innate immunity;inflammatory response