Wang Huafeng, LeBert Vanessa, Li Mengyi, Lerksuthirat Tassanee, Galles Kevin, Klein Bruce, Wüthrich Marcel
Departments of Pediatrics.
Departments of Pediatrics Department of Internal Medicine Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison.
J Infect Dis. 2016 Jun 1;213(11):1762-6. doi: 10.1093/infdis/jiw010. Epub 2016 Mar 1.
We investigated how innate sensing by the mannose receptor (MR) influences the development of antifungal immunity. We demonstrate that MR senses mannan on the surface of attenuated Blastomyces dermatitidis vaccine yeast and that MR(-/-) mice demonstrate impaired vaccine immunity against lethal experimental blastomycosis, compared with wild-type control mice. Using naive Blastomyces-specific transgenic CD4(+) T cells, we found that MR regulates differentiation of naive T cells into T-helper type 17 (Th17) effector cells, which are essential in vaccine immunity against systemic dimorphic fungi. Thus, MR regulates differentiation of Th17 cells and is required to induce vaccine immunity against lethal pulmonary blastomycosis.
我们研究了甘露糖受体(MR)的天然感知如何影响抗真菌免疫的发展。我们证明,MR可感知减毒皮炎芽生菌疫苗酵母表面的甘露聚糖,并且与野生型对照小鼠相比,MR(-/-)小鼠对致死性实验性芽生菌病的疫苗免疫受损。使用未经刺激的芽生菌特异性转基因CD4(+)T细胞,我们发现MR调节未经刺激的T细胞向17型辅助性T(Th17)效应细胞的分化,而Th17效应细胞在针对全身性双相真菌的疫苗免疫中至关重要。因此,MR调节Th17细胞的分化,并且是诱导针对致死性肺芽生菌病的疫苗免疫所必需的。