Figure 1.

The mode of action of cyclic dinucleotides (CDNs) in dendritic cells (DCs). Immunized CDNs are taken up by pinocytosis or phagocytosis by dendritic cells in vivo. In the cytoplasm, CDNs bind to STING dimers located on the endoplasmic reticulum (ER) membrane, which undergoes conformational changes and activation. The STING (Stimulator of interferon genes) activation recruits kinases TANK binding kinase 1 (TBK 1) or IκB kinase (Iκκε). TBK 1 phosphorylates interferon regulatory factor 3 (IRF3), which dimerizes and translocates to the nucleus to activate type I IFNs. Iκκε phosphorylates nuclear factor-κB (NF-κB) inhibitor IκBα leading to dissociation of IκBα from NF-κB and translocation of the later to the nucleus to activate pro-inflammatory cytokines such as TNF-α.