Characterization of the receptors for mycobacterial cord factor in Guinea pig.

Characterization of the receptors for mycobacterial cord factor in Guinea pig.
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DOI:
10.1371/journal.pone.0088747
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Yamasaki S
Yamasaki S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Toyonaga K;Miyake Y;Yamasaki S

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豚鼠是一种广泛用于研究和开发结核疫苗的动物,因为其病理学疾病过程与人类相似。我们以前曾报道过两种C型凝集素受体,Mincle(巨噬细胞诱导的C型凝集素,也称为Clec 4 e)和MCL(巨噬细胞C型凝集素,也称为Clec 4d),识别分枝杆菌索因子,海藻糖-6,6 ′-二霉菌酸酯(TDM)。在这里,我们的特点的功能的豚鼠同系物Mincle(gpMincle)和MCL(gpMCL)。gpMincle直接与TDM结合,并通过携带ITAM的接头分子FcRγ传递激活信号。而gpMCL缺乏C-末端,不能与TDM结合。在脾脏、淋巴结和腹腔巨噬细胞中检测到gpMincle的mRNA表达,并且在酵母聚糖和TDM刺激下强烈上调。gpMincle的表面表达在活化的巨噬细胞上通过新建立的单克隆抗体检测,所述单克隆抗体也具有阻断活性。该抗体有效抑制BCG感染的巨噬细胞中的TNF产生。总的来说,gpMincle是豚鼠中的TDM受体,并且TDM-Mincle轴参与针对分枝杆菌的宿主免疫应答。
Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6′-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.
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