We performed microarray experiments to compare the global transcriptional response induced by cytosolic c-di-GMP with that induced by cytosolic DNA (Fig. 1 F and Table S1 ). Whole transcriptome spotted MEEBO microarrays (Verdugo and Medrano, 2006) were used in these experiments. The results indicated that the transcriptional profile of cells stimulated by cytosolic c-di-GMP was very similar to the transcriptional profile of cells stimulated with cytosolic DNA. Induction of type I IFNs and known type I IFN-inducible genes dominated the transcriptional response, but other genes (e.g., Il6, Cd86, and Cxcl9) were also strongly induced ( Fig. 1 F and Table S1 ). Although the transcriptional profiles of cells stimulated with c-di-GMP and DNA were highly similar, a small number of genes were reproducibly preferentially induced by c-di-GMP as compared with DNA (e.g., HtrA serine peptidase 4 and claudin 23; Table S1 ). Collectively, these results suggested that similar but not identical downstream signaling pathways are triggered by DNA and c-di-GMP.