AMP-Activated Kinase (AMPK) Inhibits IFN Pathway Through Stimulator Of Interferon Genes (STING) Signaling

The homeostasis of energy metabolism plays a crucial role in the growth and function of the organism.As a regulator of cellular energy metabolism,AMP-activated protein kinase(AMPK)plays a very important role in cell proliferation,differentiation and apoptosis.Following the current research advances,the link between AMPK and signal transduction,hormone regulation,inflammation and tumorigenesis is being gradually revealed.On the other hand,the studies of cytoplasmic DNA immune-recognition pathway and its relation with tumor immunotherapy are a hot research topic in recent years.The immune response in the surveilance of foreign pathogenic microorganisms is a very energy-intensive process that affects several physiological metabolic pathways.However,the role of AMPK in innate immunity is not yet clear,which is an urgent research topic to be explored.In this study,we used CRISPR/Cas technology,Western blotting and other methods to explore AMPK regulatory mechanism in DNA-related innate immune pathway.Our experimental data show:a).In the stimulation of HT DNA and cGAMP,the expression level of IFNβ in the AMPK-/-cell lines was significantly higher than that of the wild type cell line,but this change was not obvious in the RNA signaling pathway;b).Activation of AMPK can also inhibit DNA signaling pathway;c).Compared with wild type cell lines,AMPK-/-cell lines showed the increases in STING expression at both RNA and protein levels,suggesting that AMPK inhibited the cGAS-STING pathway by inhibiting STING;d).The AMPK-/-cell line was resistant to the infection of DNA virus HSV-1 and the cells that knocked out both subtypes of a subunit were more resistant to HSV-1 than those that knocked out only one subtype.These findings provide new insights into the mechanism of AMPK fuction in the innate immune reponse.