SCD2-mediated monounsaturated fatty acid metabolism regulates cGAS-STING-dependent type I IFN in CD4+ T cells

Abstract Intimate interactions exist between the host lipid metabolism and viral responses. However, how acquired immune systems adapt lipid metabolism to meet demands and whether or not the metabolic rewiring confers a selective advantage in host immunity remains unclear. We found that viral infection attenuated the expression of genes related to lipid metabolism in CD4+ T cells, which in turn increased the anti-viral gene expression. The inhibition of the fatty acid synthesis pathway substantially increased the basal expression of anti-viral genes via the spontaneous production of type I interferon. Using a combination of CRISPR/Cas9-mediated genome editing technology and a global lipidomics analysis, we found that the decreased monounsaturated fatty acid by genetic deletion of Scd2 was crucial for the induction of an anti-viral response through the activation of cGAS-STING pathway. These findings demonstrate the novel relationship between fatty acid biosynthesis and type I IFN responses that enhances the anti-viral response.