IFN-alpha/beta Signaling Is Required for CDG-Mediated CTL Generation and B Lymphocyte Activation

Among cyclic di-nucleotides (CDN), both cyclic di-AMP (CDA) and di-GMP (CDG) are promising adjuvants and immune modulators. These molecules are not only able to induce profuse antibody production but also predominant T helper 1 and cytotoxic CD8 T lymphocytes (CTL) responses, which enable their use for vaccination against intracellular pathogens as well as in cancer immunotherapy. However, for their successful translation into the clinic, a comprehensive understanding of CDN mode of action is still essential. Consistent with evidence in the literature, we show here that IFN-alpha/beta (Type I IFN) is crucial for CDG-mediated B cell activation. We recently determined the key role of type I IFN signaling for CDA-mediated enhancement of immunogenicity. Based on the biological activities of type I IFN, in this study, we hypothesized that it might also be required for CTL induction by CDG. We disclose here the mode of action of type I IFN signaling in CDG-mediated cross-presentation and subsequent CTL generation.