transcription factors, as well as phosphorylation of the p38, JNK, and ERK MAP kinases, in response to c-di-GMP. Activation of IRF3 involves phosphorylation, dimerization, and translocation into the nucleus. We tested whether treatment with c-di-GMP resulted in significant nuclear accumulation of IRF3. As expected, we found that c-di-GMP resulted in significant translocation of IRF3 to the nucleus (Fig. 3 A) .