Nile tilapia DNA sensor STING is involved in the IFN-β and AP-1 signaling pathways in the immune response dependent on DDX41.

Stimulator of interferon genes (STING) plays important roles in innate immunology. In this study, we isolated the STING gene in Nile tilapia, termed OnSTING. Using quantitative RT-PCR, we explored the expression patterns of the OnSTING gene. Using dual-luciferase reporter assays, we revealed the effect of STING overexpression on nuclear factor κB (NF-κB), IFN and AP activation in HEK 293 cells. Using coimmunoprecipitation, the interaction of STING and TRIF was studied. The effect of OnSTING overexpression on the antibacterial activity in tilapia was investigated. The results showed that upon stimulation with Streptococcus agalactiae, the OnSTING transcript was upregulated in all the tested tissues. OnSTING mRNA levels were very stable from 2.5 to 8.5 dpf. Moreover, OnSTING, OnIFN and IRF3 expression was induced by LPS, Poly (I:C), S. agalactiae WC1535 and DCPS in Nile tilapia macrophages. Overexpression of OnSTING and OnDDX41 increased NF-κB activation in HEK293T cells and slightly increased IFN-β activation but had no effect on AP-1 activation. OnSTING interacted with OnDDX41 and OnTBK1. However, OnSTING did not interact with TRIF. OnSTING overexpression in vivo decreased the sensitivity of tilapia to S. agalactiae infection. These results are helpful for clarifying the innate immune response against bacterial infection in Nile tilapia.