Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.
Cutting edge: Mincle is essential for recognition and adjuvanticity of the mycobacterial cord factor and its synthetic analog trehalose-dibehenate.
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DOI：
10.4049/jimmunol.0904013
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发表时间：
2010-03-15
期刊：
影响因子：
--
通讯作者：
Lang R
中科院分区：
文献类型：
--
作者：
Schoenen H;Bodendorfer B;Hitchens K;Manzanero S;Werninghaus K;Nimmerjahn F;Agger EM;Stenger S;Andersen P;Ruland J;Brown GD;Wells C;Lang R
分枝杆菌脐带因子海藻糖-6，6-二霉菌酸酯（TDM）及其合成类似物海藻糖-6，6-二山嵛酸酯（TDB）是Th 1/Th 17疫苗接种的有效佐剂，可激活抗原呈递细胞中的Syk-Card 9信号传导。在此，我们进一步研究了TDM和TDB激活先天免疫的分子机制。Syk偶联衔接蛋白Fc受体γ链（FcRγ）对巨噬细胞活化和Th 17佐剂活性至关重要。FcRγ相关的C型凝集素受体Mincle在巨噬细胞中表达，并被TDM和TDB上调。重组Mincle-Fc融合蛋白特异性结合糖脂。Mincle的基因消除消除了TDM/TDB诱导的巨噬细胞活化和对结核亚单位疫苗的T细胞免疫应答的诱导。缺乏Mincle或FcRγ的巨噬细胞在对牛分枝杆菌BCG的炎症反应中受损。这些结果证实Mincle是分枝杆菌索状因子的关键受体，并控制TDM和TDB的Th 1/Th 17佐剂性。
The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analogue trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in antigen presenting cells. Here, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein Fc receptor gamma chain (FcRγ) was essential for macrophage activation and Th17 adjuvanticity. The FcRγ-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 FcRγ were impaired in the inflammatory response to Mycobacterium bovis BCG. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.
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