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

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.