Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax.
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.
Datta
Sandip K
SK
Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. dattas@niaid.nih.gov
Sabet
Mojgan
M
Nguyen
Kim Phung L
KP
Valdez
Patricia A
PA
Gonzalez-Navajas
Jose M
JM
Islam
Shamima
S
Mihajlov
Ivan
I
Fierer
Joshua
J
Insel
Paul A
PA
Webster
Nicholas J
NJ
Guiney
Donald G
DG
Raz
Eyal
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D022122:Anthrax Vaccines / Q000276:immunology*; D000917:Antibody Formation; D002772:Cholera Toxin / Q000276:immunology* / Q000494:pharmacology; D018928:Immunity, Mucosal; D001239:Inhalation; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D020381:Interleukin-17; D002772:Cholera Toxin