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

被引：125

作者：

Datta, Sandip K. ^{[1
]}

Sabet, Mojgan ^{[2
]}

Nguyen, Kim Phung L. ^{[2
]}

Valdez, Patricia A. ^{[1
]}

Gonzalez-Navajas, Jose M. ^{[2
]}

Islam, Shamima ^{[1
]}

Mihajlov, Ivan ^{[2
]}

Fierer, Joshua ^{[2
,4
]}

Insel, Paul A. ^{[2
,3
]}

Webster, Nicholas J. ^{[2
]}

Guiney, Donald G. ^{[2
]}

Raz, Eyal ^{[2
]}

机构：

[1] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA

[2] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[4] Vet Affairs Healthcare, Dept Infect Dis, San Diego, CA 92161 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 23期

基金：

美国国家卫生研究院;

关键词：

IL-17; dendritic cell; T cell; vaccine; cAMP; ARYL-HYDROCARBON RECEPTOR; T-HELPER-CELLS; INTERLEUKIN-17; PRODUCTION; BACILLUS-ANTHRACIS; CUTTING EDGE; CYCLIC-AMP; DIFFERENTIATION; MICE; AUTOCRINE; IL-21;

D O I：

10.1073/pnas.1002348107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 requiresc AMP-dependent secretion of IL-1 beta 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.

引用

页码：10638 / 10643

页数：6

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