Interferon-α2b against microbes through promoting biosynthesis of unsaturated fatty acids

Interferon (IFN) family is a large group of cytokines involved in innate immune response against various microorganisms. However, whether IFN functions in antimicrobial property by metabolic pathways is largely unknown. In the present study, GC-MS-based metabolome is investigated in humoral fluid of zebrafish (Danio rerio) which are exposed to three doses of IFN-α2b, designed as IFN-L, IFN-M, and IFN-H. Out of 67 compounds identified, 19, 28, and 29 differential abundances of metabolites are identified in the three groups compared with control, respectively. A total of 41 differential metabolites constructed IFN-dependent metabolome, in which 13 overlap among the three doses of IFN-α2b groups. These overlapped metabolites show that decreased alanine asparate and glutamate metabolic pathway, arginine and proline metabolic pathway, and increased purine metabolism form a characteristic feature in response to IFN-α2b. Further dose-related metabolites indicate that biosynthesis of unsaturated fatty acids is enriched only in IFN-M and IFN-H, which is related to high protection against bacterial infection. Exogenous fatty acids, especially unsaturated linoleic acid, may elevate the survival ability of zebrafish infected with extracellular pathogenic V. alginolyticus and intracellular pathogenic Edwardsiella tarda. These results disclose an unknown mechanism by which IFN-α2b protects host from microbial infections. Our findings highlight the ways to understand action of IFN in content of metabolic regulation.