The Finding Of A Carbohydrate That Affects The CGAS-STING Innate Immune Signaling Pathway And The Research On Its Mechanism

Previous research has demonstrated that glucose metabolism can affect the innate immune response mediated by RLRs,however it cannot affect the innate immune response mediated by cGAS-STING.Therefore,we wonder whether there exists one kind of carbohydrate whose metabolism can affect the innate immune response mediated by cGAS-STING.We chose eight kinds of carbohydrates,which are fructose,mannose,galactose,glucose,sucrose,trehalose,maltose and lactose,and tested whether they can affect the production of cytokine mediated by cGAS-STING signaling pathway.The results shown that fructose can markedly increase the expression level of IFN-β and CXCL10 in THP-1.Both glucose and fructose can metabolize through hexokinase(HK),while ketohexokinase(KHK)is specialized for fructose metabolism.We found that KHK can also increase the expression of IFN-β and CXCL10 mediated by the activation of the cGAS-STING pathway,and the overexpression of STING can further enhance this increase.Through further research we found that KHK can interact with STING when the cGAS-STING pathway is activated,in the mean time,KHK enhanced the collaboration of IRF3 by STING,which leads to the enhancement of the innate immune response mediated by cGAS-STING.