Research Articles

DNA was known to stimulate immune responses long before it was shown to be a genetic material, but the mechanism by which DNA func-tions as an immune stimulant remains poorly understood (1). Although DNA can stimulate the production of type-I interferons in dendritic cells through binding to Toll-like receptor 9 (TLR9) in the endosome, how DNA in the cytosol induces IFN is still unclear. In particular, the sensor that detects cytosolic DNA in the interferon pathway remains elusive (2). Although several proteins, including DAI, RNA polymerase III, IFI16, DDX41 and several other DNA helicases, have been suggested to func-tion as the potential DNA sensors that induce IFN, none has been met with universal acceptance (3). Purification and identification of cyclic GMP-AMP synthase (cGAS). We showed that delivery of DNA to mammalian cells or cyto-solic extracts triggered the production of cyclic GMP-AMP (cGAMP), which bound to and activated STING, leading to the activation of IRF