| First Author | Blaauboer SM | Year | 2015 |
| Journal | Elife | Volume | 4 |
| PubMed ID | 25898005 | Mgi Jnum | J:269464 |
| Mgi Id | MGI:6204319 | Doi | 10.7554/eLife.06670 |
| Citation | Blaauboer SM, et al. (2015) The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo. Elife 4 |
| abstractText | 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, IFNgamma, IL-5, IL-13, IL-23, and IL-6 production in vivo. Notably, CDG induces IFNlambda, but not IFNbeta, in vivo. Our study revealed previously unrecognized in vivo functions of MPYS and advanced our understanding of CDG as a mucosal vaccine adjuvant. |
