Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10638-43. doi: 10.1073/pnas.1002348107. Epub 2010 May 17.
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.
霍乱毒素（CT）作为疫苗佐剂在小鼠中引发黏膜免疫应答。但其发挥佐剂作用的机制尚不完全清楚。我们发现，用辐照孢子疫苗预防吸入性炭疽依赖于 CT 介导的产生白细胞介素-17 的 CD4 Th17 细胞的诱导。此外，白细胞介素-17 参与 CT 诱导的血清和黏膜抗体应答。与由白细胞介素-6 和转化生长因子-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 诱导它们需要树突状细胞依赖 cAMP 的白细胞介素-1β和降钙素基因相关肽的分泌。这些发现表明 Th17 细胞介导 CT 的黏膜佐剂效应，并确定了以前未探索的参与 Th17 诱导的途径，这些途径可能成为开发独特黏膜佐剂的目标。
