1. Cell Biology
  2. Immunology and Inflammation
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The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo

Research Article
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Cite this article as: eLife 2015;4:e06670 doi: 10.7554/eLife.06670

Abstract

Effective mucosal adjuvants enhance the magnitude and quality of the vaccine response. Cyclic di-GMP is a promising mucosal vaccine adjuvant. However, its in vivo mechanisms are unclear. Here, we showed,in mice, that cyclic di-GMP elicits stronger Ab and TH responses than the mammalian 2'3'-cyclic GMP-AMP, and generated better protection against Streptococcus pneumoniae infection than 2'3'-cyclic GMP-AMP adjuvanted vaccine. We identified two in vivo mechanisms of cyclic di-GMP. First, intranasally administered cyclic di-GMP 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 cyclic di-GMP selectively activated pinocytosis-efficient-DCs, leading to TH polarizing cytokines IL-12p70, IFNγ, IL-5, IL-13, IL-23,and IL-6 production in vivo. Notably, cyclic di-GMP induces IFNλ, but not IFNβ, in vivo. Our study revealed previously unrecognized in vivo functions of MPYS and advanced our understanding of cyclic di-GMP as a mucosal vaccine adjuvant.

Article and author information

Author details

  1. Steven M Blaauboer

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Samira Mansouri

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Heidi R Tucker

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hatti L Wang

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vincent D Gabrielle

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Lei Jin

    Center for Immunology and Microbial Disease, Albany Medical College, Albany, United States
    For correspondence
    JINL@MAIL.amc.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments with mice were performed in accordance to the regulations and approval of Albany Medical College (Albany, NY) and the Institutional Animal Care and Use Committee, ACUP NO: 1208002.

Reviewing Editor

  1. Fiona M Powrie, Oxford University, United Kingdom

Publication history

  1. Received: January 25, 2015
  2. Accepted: April 21, 2015
  3. Accepted Manuscript published: April 21, 2015 (version 1)
  4. Version of Record published: May 12, 2015 (version 2)

Copyright

© 2015, Blaauboer et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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