Inducible MicroRNA-217 Inhibits NF-κB- and IRF3-Driven Immune Responses in Lower Vertebrates through Targeting TAK1.

Upon recognition of bacterial or viral components by pattern recognition receptors, cells could be activated to produce inflammatory cytokines, type I IFN, and IFN-stimulated genes. These antibacterial and antiviral immunities are tightly regulated by the host to prevent inappropriate immune responses. MicroRNAs (miRNAs) have emerged as an essential regulatory network with profound effects on mammalian inflammation and immune responses, but the regulatory networks of miRNA-mediated immune response in lower vertebrates remain largely unknown. In this study, we report a miRNA, miR-217, identified from miiuy croaker, which plays a negative role in host antiviral and antibacterial immunity. We found that miR-217 could be abundantly expressed upon Gram-negative bacteria, as well as rhabdovirus infection. Inducible miR-217 suppresses the production of inflammatory cytokines and type I IFN by targeting TAK1, thereby avoiding excessive inflammation. Particularly, we revealed that miR-217 modulates the antibacterial and antiviral immunity through TAK1-mediated NF-κB and IRF3 signaling pathways. The collective results indicate that miR-217 acts as a negative feedback regulator involved in host antibacterial and antiviral immune responses, which will provide insights into the intricate networks of host-virus interaction in lower vertebrates.