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Elife. 2015 Apr 21;4. doi: 10.7554/eLife.06670.

The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo.

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Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States.


Effective mucosal adjuvants enhance the magnitude and quality of the vaccine response. Cyclic di-GMP (CDG) is a promising mucosal vaccine adjuvant. However, its in vivo mechanisms are unclear. Here, we showed, in mice, that CDG elicits stronger Ab and TH responses than the mammalian 2'3'-cyclic GMP-AMP (cGAMP), and generated better protection against Streptococcus pneumoniae infection than 2'3'-cGAMP adjuvanted vaccine. We identified two in vivo mechanisms of CDG. First, intranasally administered CDG greatly enhances Ag uptake, including pinocytosis and receptor-mediated endocytosis in vivo. The enhancement depends on MPYS (STING, MITA) expression in CD11C(+) cells. Second, we found that CDG selectively activated pinocytosis-efficient-DCs, leading to T(H) polarizing cytokines IL-12p70, IFNγ, IL-5, IL-13, IL-23, and IL-6 production in vivo. Notably, CDG induces IFNλ, but not IFNβ, in vivo. Our study revealed previously unrecognized in vivo functions of MPYS and advanced our understanding of CDG as a mucosal vaccine adjuvant.


STING; cell biology; dendritic cells; immunology; lung; mouse; mucosal adjuvant; pneumococcal vaccine

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