Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax
Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax
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DOI：
10.1073/pnas.1002348107
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发表时间：
2010-06-08
影响因子：
11.1
通讯作者：
Raz, Eyal
中科院分区：
文献类型：
--
作者：
Datta, Sandip K.;Sabet, Mojgan;Raz, Eyal
霍乱毒素（CT）用作疫苗佐剂时会引起小鼠粘膜免疫反应。 CT 发挥其辅助作用的机制尚不完全清楚。我们表明，辐照孢子疫苗对吸入性炭疽的保护作用取决于 CT 介导的产生 IL-17 的 CD4 Th17 细胞的诱导。此外，IL-17 还参与 CT 诱导的血清和粘膜抗体反应。与IL-6和TGF-β诱导的Th17细胞相比，CT诱导的Th17细胞具有独特的细胞因子谱，并且CT诱导的Th17细胞需要树突状细胞依赖AMP分泌IL-1β和β-降钙素基因相关肽。这些发现表明，Th17 细胞介导 CT 的粘膜佐剂作用，并确定了先前未探索的参与 Th17 诱导的途径，这些途径可以作为开发独特粘膜佐剂的目标。
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.