A Single ssDNA Aptamer Binding to Mannose-Capped Lipoarabinomannan of Bacillus Calmette-Guerin Enhances Immunoprotective Effect against Tuberculosis
A Single ssDNA Aptamer Binding to Mannose-Capped Lipoarabinomannan of Bacillus Calmette-Guerin Enhances Immunoprotective Effect against Tuberculosis
复制标题
与卡介苗甘露糖封端的脂阿拉伯甘露聚糖结合的单个 ssDNA 适体可增强针对结核病的免疫保护作用。
DOI：
10.1021/jacs.6b05357
复制
发表时间：
2016-09-14
影响因子：
15
通讯作者：
Zhang, Xiao-Lian
中科院分区：
文献类型：
--
作者：
Sun, Xiaoming;Pan, Qin;Zhang, Xiao-Lian
由于牛分枝杆菌（Mycobacterium bovis），称为卡介苗（bacillus Calmette-Guerin，BCG），是唯一可用的使用的结核（TB）疫苗，保留了限制其保护性免疫原性的免疫调节特性，因此存在持续的努力来鉴定免疫抑制机制以及用于改善BCG的免疫原性的新策略。在此，选择特异性结合BCG的甘露糖封端的脂阿拉伯甘露聚糖（ManLAM）的ssDNA适体“抗体”BM 2。BM 2显著阻断ManLAM-甘露糖受体（MR）结合，触发ManLAM-CD 44信号传导，并通过细胞表面CD 44在体外和体内增强M1巨噬细胞和Th 1活化。在小鼠和猴模型中，BM 2增强BCG对强毒结核分枝杆菌H37 Rv感染的免疫保护作用。因此，我们报道了ManLAM与CD 44在巨噬细胞和CD 4（+）T细胞上相互作用的新机制，并揭示了ManLAM结合膜分子CD 44是增强BCG免疫原性的新靶点，而BM 2具有作为BCG免疫增强剂的强大潜力。
Because Mycobacterium bovis, termed bacillus Calmette-Guerin (BCG), the only available used tuberculosis (TB) vaccine, retains immunomodulatory properties that limit its protective immunogenicity, there are continuous efforts to identify the immunosuppression mechanism as well as new strategies for improving the immunogenicity of BCG. Here, an ssDNA aptamer "antibody" BM2 specifically bound to the mannose-capped lipoarabinomannan (ManLAM) of BCG was Selected. BM2 significantly blocked ManLAM-mannose receptor (MR) binding, triggered ManLAM-CD44 signaling, and enhanced M1 macrophage and Th1 activation via cellular surface CD44 in vitro and in vivo. BM2 enhanced immunoprotective effects of BCG against virulent Mycobacterium tuberculosis H37Rv infection in mice and monkeys models. Thus, we report a, new mechanism of the interaction between ManLAM and CD44 on macrophages and CD4(+) T cells and reveal that ManLAM-binding Membrane molecule CD44 is a novel target for the enhancement of BCG immunogenicity, and BM2 has strong potential as an immune enhancer for BCG.