前沿：Mincle 对于分枝杆菌 Cord 因子及其合成类似物海藻糖二硬脂酸酯的识别和佐剂活性至关重要。
Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.
机构信息
Institute of Clinical Microbiology, Immunology and Hygiene Medical Department, Friedrich-Alexander-Universität Erlangen-Nürnberg and University Clinics of Erlangen, Erlangen, Germany.
出版信息
J Immunol. 2010 Mar 15;184(6):2756-60. doi: 10.4049/jimmunol.0904013. Epub 2010 Feb 17.
Abstract
The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRgamma was essential for macrophage activation and Th17 adjuvanticity. The FcRgamma-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRgamma were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.
摘要
分枝杆菌 cord 因子海藻糖-6,6-二没食子酸酯 (TDM) 和其合成类似物海藻糖-6,6-二油酰基酯 (TDB) 是 Th1/Th17 疫苗接种的有效佐剂，可激活 APC 中的 Syk-Card9 信号通路。在这项研究中，我们进一步研究了 TDM 和 TDB 对先天免疫激活的分子机制。Syk 偶联衔接蛋白 FcRγ 对于巨噬细胞的激活和 Th17 的佐剂活性是必不可少的。FcRγ 相关的 C 型凝集素受体 Mincle 在巨噬细胞中表达，并可被 TDM 和 TDB 上调。重组 Mincle-Fc 融合蛋白特异性结合糖脂。Mincle 的基因缺失消除了 TDM/TDB 诱导的巨噬细胞激活和对结核亚单位疫苗的 T 细胞免疫反应的诱导。缺乏 Mincle 或 FcRγ 的巨噬细胞在对牛分枝杆菌卡介苗的炎症反应中受损。这些结果表明 Mincle 是分枝杆菌 cord 因子的关键受体，控制 TDM 和 TDB 的 Th1/Th17 佐剂活性。
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