Global transcriptional changes in response to cGAMP depend on STING in human THP-1 cells

Cytosolic detection of foreign or misplaced self-DNA through the cGAS-STING pathway leads to cGAS-mediated synthesis of the second messenger molecule cGAMP.The immune signaling molecule STING binds cGAMP directly,and thus functions as a cGAMP sensor.Binding of cGAMP induces the activation of STING with the subsequent induction of anti-viral and proinflammatory genes.Currently,it is not known whether STING is the only cellular sensor of cGAMP,and it has not been reported whether stimulation with cGAMP can induce gene transcription independently of STING.Here we analyzed the global cGAMP-induced transcriptional gene program in STING-deficient human monocyte-derived THP-1 cells.We found that the global cGAMP-induced transcriptional response was dependent on STING and failed to identify groups of genes that were affected by cGAMP in the absence of STING.Our data therefore strongly indicate that STING is the sole receptor for cGAMP in human macrophages.