Fig. 1.

Immunomodulatory effects of IFN-I signaling. ①: RIG-I and MDA5, members of the PRR, are major cytoplasmic RNA sensors that, upon ligand binding, sequentially activate downstream axes to produce phosphorylated IRF3; ②: STING is phosphorylated by TBK1 in response to DNA stimulation. DNA in the cytoplasm activates cGAS to produce the second messenger cGAMP, which then binds to STING and activates STING, and active STING then directly recruits and activates TBK1, resulting in phosphorylated IRF3; ③: LPS stimulation activates TLR4, which in turn activates the adaptor protein MyD88 (not shown) and TRIF. TRIF activates TBK1, which in turn phosphorylates TRIF at consensus motifs. phosphorylated TRIF then recruits IRF3, which promotes phosphorylation of IRF3 by TBK1. Phosphorylated IRF3 dimerizes through the same positively charged surface. The IRF3 dimer then enters the nucleus and, together with NF-κB, initiates the production of type I interferons. After secretion, IFN-I interferons exert effects on various cells through different mechanisms. APRIL (official name TNFSF13), TNF superfamily member 13; cAMP cyclic AMP, GZMB granzyme B, EMT epithelial-to-mesenchymal transition, MDSC myeloid-derived suppressor cell, NK natural killer, NOS2 nitric oxide synthase 2, PRF1 perforin 1