The cGAS-STING pathway and its functions in immune defense and inflammatory regulation in teleost fish.

Cyclic GMP-AMP synthase (cGAS) could recognize double-stranded DNA in the cytoplasm and catalyze the synthesis of cyclic GMP-AMP (cGAMP). This molecule activates the endoplasmic reticulum-resident protein stimulator of interferon genes (STING), thereby initiating the TBK1 (TANK-binding kinase 1)-IRF3 (interferon regulatory factor 3) signal cascade and promoting the expression of type I interferons and various inflammatory factors. The cGAS-STING pathway serves as a fundamental signal axis for DNA recognition in the cytoplasm of vertebrates and is crucial for innate immune defense. Recent research on the cGAS-STING pathway in fish has gradually advanced, with gene cloning and analyses completed across various fish species, indicating that this pathway plays a significant role in antiviral responses in fish. However, compared to mammals, the cGAS-STING pathway exhibits relative deficiencies in molecular regulatory mechanisms, structural analyses, and in vivo functional validations in different aquatic animals. Teleost fish occupy a critical stage in vertebrate evolution. The cGAS-STING pathway in teleost fish is systematically summarized to enhance our comprehensive understanding for the innate immune regulatory network, and the potential molecular targets is to be identified for disease-resistant breeding, immune enhancement, and sustainable aquaculture practices.