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Insights into Interactions of Mycobacteria with the Host Innate Immune System from a Novel Array of Synthetic Mycobacterial Glycans
ACS Chemical Biology ( IF 4 ) Pub Date : 2017-11-03 00:00:00 , DOI: 10.1021/acschembio.7b00797
Ruixiang Blake Zheng,Sabine A. F. Jégouzo,Maju Joe,Yu Bai,Huu-Anh Tran,Ke Shen,Jörn Saupe,Li Xia,Md. Faiaz Ahmed,Yu-Hsuan Liu,Pratap Subhashrao Patil,Ashish Tripathi,Shang-Cheng Hung,Maureen E. Taylor,Todd L. Lowary,Kurt Drickamer

An array of homogeneous glycans representing all the major carbohydrate structures present in the cell wall of the human pathogen Mycobacterium tuberculosis and other mycobacteria has been probed with a panel of glycan-binding receptors expressed on cells of the mammalian innate immune system. The results provide an overview of interactions between mycobacterial glycans and receptors that mediate uptake and survival in macrophages, dendritic cells, and sinusoidal endothelial cells. A subset of the wide variety of glycan structures present on mycobacterial surfaces interact with cells of the innate immune system through the receptors tested. Endocytic receptors, including the mannose receptor, DC-SIGN, langerin, and DC-SIGNR (L-SIGN), interact predominantly with mannose-containing caps found on the mycobacterial polysaccharide lipoarabinomannan. Some of these receptors also interact with phosphatidyl-myo-inositol mannosides and mannose-containing phenolic glycolipids. Many glycans are ligands for overlapping sets of receptors, suggesting multiple, redundant routes by which mycobacteria can enter cells. Receptors with signaling capability interact with two distinct sets of mycobacterial glycans: targets for dectin-2 overlap with ligands for the mannose-binding endocytic receptors, while mincle binds exclusively to trehalose-containing structures such as trehalose dimycolate. None of the receptors surveyed bind furanose residues, which often form part of the epitopes recognized by antibodies to mycobacteria. Thus, the innate and adaptive immune systems can target different sets of mycobacterial glycans. This array, the first of its kind, represents an important new tool for probing, at a molecular level, biological roles of a broad range of mycobacterial glycans, a task that has not previously been possible.

中文翻译:

从新型的合成分枝杆菌聚糖阵列深入了解分枝杆菌与宿主先天免疫系统的相互作用。

代表人类病原体结核分枝杆菌细胞壁中所有主要碳水化合物结构的均质聚糖阵列已经用在哺乳动物先天免疫系统细胞上表达的一组聚糖结合受体来探测其他分枝杆菌和其他分枝杆菌。该结果概述了分枝杆菌聚糖与介导巨噬细胞,树突状细胞和正弦血管内皮细胞摄取和存活的受体之间的相互作用。分枝杆菌表面上存在的多种聚糖结构的子集通过测试的受体与先天免疫系统的细胞相互作用。内吞受体,包括甘露糖受体,DC-SIGN,兰格宁和DC-SIGNR(L-SIGN),主要与在分枝杆菌多糖lipoarabinomannan上发现的含甘露糖的帽相互作用。这些受体中的一些也与磷脂酰肌反应。-肌醇甘露糖苷和含甘露糖的酚糖脂。许多聚糖是受体重叠组的配体,表明分枝杆菌可以进入细胞的多种冗余途径。具有信号传导功能的受体与两种不同的分枝杆菌聚糖相互作用:dectin-2的靶标与结合甘露糖的内吞受体的配体重叠,而小胶束仅与含海藻糖的结构(如海藻糖二甲酸酯)结合。被调查的受体均未结合呋喃糖残基,后者经常形成分枝杆菌抗体识别的表位的一部分。因此,先天性和适应性免疫系统可以靶向不同组的分枝杆菌聚糖。该阵列是第一个此类阵列,代表了一种重要的新工具,可以在分子水平上进行探测,
更新日期:2017-11-03
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