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Direct interaction between cholera toxin and dendritic cells is required for oral adjuvant activity

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Author

Summary, in English

Cholera toxin (CT) binds to GM1-ganglioside receptors present on all nucleated cells. Despite this, it is a very potent mucosal adjuvant that has a dramatic impact on immune cells, as well as nerve and epithelial cells, causing diarrhea. This fact has hampered our understanding of whether the adjuvanticity of CT is direct or indirect, as cells that bind CT may or may not be involved in its adjuvant function. The mucosal barrier is maintained by tight junctions between epithelial cells but dendritic cells (DCs) can protrude luminal dendrites. Here we investigated which cells are involved in the immune augmenting effect of CT. We explored oral immunizations with ovalbumin (OVA) and CT in bone marrow chimeric mice deficient in GM1-ganglioside in defined cellular subsets. We found that chimeric mice lacking GM1 in nonhematopoietic cells, including epithelial cells, mounted an unaltered intestinal IgA response. In contrast, chimeric mice lacking GM1-expressing hematopoietic cells in general, or specifically GM1-expressing conventional DCs (cDCs), largely failed to elicit anti-OVA adaptive immune responses. Therefore, the adjuvanticity of CT does not require epithelial activation, but is directly dependent on the binding of CT to gut cDCs via GM1-ganglioside. These results could have important implications for the generation of novel oral adjuvants.

Department/s

Publishing year

2013

Language

English

Pages

1779-1788

Publication/Series

European Journal of Immunology

Volume

43

Issue

7

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Immunology in the medical area

Keywords

  • Cholera toxin
  • DC
  • IgA
  • Mucosal immunity
  • Oral adjuvants

Status

Published

Research group

  • Adaptive Immunity

ISBN/ISSN/Other

  • ISSN: 1521-4141