New Insights into the Crosstalk among the Interferon and Inflammatory Signaling Pathways in Response to Viral Infections: Defense or Homeostasis

Innate immunity plays critical roles in eliminating viral infections, healing an injury, and restoring tissue homeostasis. The signaling pathways of innate immunity, including interferons (IFNs), nuclear factor kappa B (NF-κB), and inflammasome responses, are activated upon viral infections. Crosstalk and interplay among signaling pathways are involved in the complex regulation of antiviral activity and homeostasis. To date, accumulating evidence has demonstrated that NF-κB or inflammasome signaling exhibits regulatory effects on IFN signaling. In addition, several adaptors participate in the crosstalk between IFNs and the inflammatory response. Furthermore, the key adaptors in innate immune signaling pathways or the downstream cytokines can modulate the activation of other signaling pathways, leading to excessive inflammatory responses or insufficient antiviral effects, which further results in tissue injury. This review focuses on the crosstalk between IFN and inflammatory signaling to regulate defense and homeostasis. A deeper understanding of the functional aspects of the crosstalk of innate immunity facilitates the development of targeted treatments for imbalanced homeostasis.