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Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10638-43. doi: 10.1073/pnas.1002348107. Epub 2010 May 17.

Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax.

Author information

1
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dattas@niaid.nih.gov

Abstract

Cholera toxin (CT) elicits a mucosal immune response in mice when used as a vaccine adjuvant. The mechanisms by which CT exerts its adjuvant effects are incompletely understood. We show that protection against inhalation anthrax by an irradiated spore vaccine depends on CT-mediated induction of IL-17-producing CD4 Th17 cells. Furthermore, IL-17 is involved in the induction of serum and mucosal antibody responses by CT. Th17 cells induced by CT have a unique cytokine profile compared with those induced by IL-6 and TGF-beta, and their induction by CT requires cAMP-dependent secretion of IL-1beta and beta-calcitonin gene-related peptide by dendritic cells. These findings demonstrate that Th17 cells mediate mucosal adjuvant effects of CT and identify previously unexplored pathways involved in Th17 induction that could be targeted for development of unique mucosal adjuvants.

PMID:
20479237
PMCID:
PMC2890829
DOI:
10.1073/pnas.1002348107
[Indexed for MEDLINE]
Free PMC Article

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