Biological DNA Sensor: Chapter 13. Adjuvants Targeting the DNA Sensing Pathways – Cyclic-di-GMP and other Cyclic-Dinucleotides

Cyclic dinucleotides (c-di-NMPs), such as c-di-GMP and c-di-AMP were first discovered in bacteria, where they play important roles as second messenger molecules that regulate bacterial cellular functions. In addition, these and other c-di-NMPs exert potent biological effects on mammalian cells, such as the inhibition of cancer cell proliferation, immune cell activation, and the triggering of type I interferon production. Here, we introduce the biology of c-di-NMPs in bacterial systems and review the current state of the literature on their biological effects in mammalian cells. Emphasis is placed on evaluating the evidence that c-di-NMPs have potent immune stimulatory effects on cultured mouse and human cells and can act as adjuvants and immune stimulants in animal models. In addition, we highlight areas where further experimentation could hasten the development of c-di-NMPs as adjuvants in potent and safe systemic and mucosal vaccines.