Figure 1. Cyclic GMP-AMP signaling in the immune response. Although cytosolic DNA (a) has long been known to trigger an immune response, it was only this year that its primary molecular sensor was identified. The sensor, cyclic GMP-AMP synthase (cGAS), is activated by binding directly to DNA, and it subsequently synthesizes cyclic GMP-AMP (cGAMP) from ATP and GTP (b). cGAMP is a soluble molecule that can be transmitted from cell to cell between tight junctions. It directly binds to transmembrane protein 173 (STING; TMEM173), triggering a signaling cascade that leads to the production of type I interferon (c).

There are two therapeutic options for manipulating the pathway. To stimulate an immune response against a foreign infection, cGAMP could be given as an adjuvant that induces a type I interferon response. To prevent inflammation, which can be caused by host DNA entering the cytoplasm, inhibitors of cGAMP could be developed.