c-di-GMP - STING Agonist

c-di-GMP bacterial cyclic di-nucleotide - STING ligand

Bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) is a second messenger produced in bacteria but not in mammals. This cyclic dinucleotide is involved in complex biological processes, such as biofilm formation, virulence and photosynthesis.

Besides its role as an intracellular and intercellular signaling molecule in prokaryotes, c-di-GMP also affects eukaryotes.

In mammals, c-di-GMP is recognized by STING, initiating a response characterized by the production of type I IFNs through the TBK1/IRF3 axis [1, 2]. The helicase DDX41 may play a role in the recognition of c-di-GMP upstream of STING [3].

Recent studies have also demonstrated that c-di-GMP exhibits potent adjuvant properties [4].

References

1. Jin L. et al., 2011. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 187(5):2595-601.
2. Burdette DL. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 478(7370):515-8.
3. Parvatiyar K. et al., 2012 The helicase DDX41 recognizes the bacterial secondary messengers cyclic di-GMP and cyclic di-AMP to activate a type I IFN immune response. Nat. Immunol.13(12):1155-61.
4. Madhun AS. et al., 2011. Intranasal c-di-GMP-adjuvanted plant-derived H5 influenza vaccine induces multifunctional Th1 CD4+ cells and strong mucosal and systemic antibody responses in mice. Vaccine.29(31):4973-82.