Identification of Mycobacterial α-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation
Identification of Mycobacterial α-Glucan As a Novel Ligand for DC-SIGN: Involvement of Mycobacterial Capsular Polysaccharides in Host Immune Modulation
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DOI：
10.4049/jimmunol.0900768
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发表时间：
2009-10-15
影响因子：
4.4
通讯作者：
Appelmelk, Ben J.
中科院分区：
文献类型：
--
作者：
Geurtsen, Jeroen;Chedammi, Sunita;Appelmelk, Ben J.
结核分枝杆菌具有多种影响宿主免疫应答的免疫调节因子。当芽孢杆菌遇到它的靶细胞时，它的细胞包膜的最外面的成分是第一个相互作用的。分枝杆菌，包括M.结核病，被主要由蛋白质和多糖组成的松散附着的包膜包围。虽然胶囊的化学成分研究得相对较好，但其生物学功能却知之甚少。本研究的目的是通过鉴定识别其成分的宿主受体来进一步评估分枝杆菌荚膜的功能作用。我们专注于α-葡聚糖，这是占主导地位的荚膜多糖。在这里，我们证明了M。结核α-葡聚糖是C型凝集素DC-SIGN（树突细胞特异性ICAM-3-抓取非整联蛋白）的新型配体。通过使用相关的糖原结构，我们发现DC-SIGN对α-葡聚糖的识别是一个普遍的特征，并且这种相互作用是由内部葡萄糖残基介导的。至于甘露糖加帽的脂阿拉伯甘露聚糖，一种丰富的分枝杆菌细胞壁相关糖脂，α-葡聚糖与DC-SIGN的结合刺激了LPS激活的单核细胞衍生的树突细胞产生免疫抑制性IL-10。通过使用特异性抑制剂，我们表明这种IL-10诱导是DC-SIGN依赖性的，并且还需要NF-κ B的乙酰化。最后，我们证明了纯化的M.与已报道的真菌α-葡聚糖相反，结核α-葡聚糖不能激活TLR 2。免疫学杂志，2009，183：5221-5231.
Mycobacterium tuberculosis possesses a variety of immunomodulatory factors that influence the host immune response. When the bacillus encounters its target cell, the outermost components of its cell envelope are the first to interact. Mycobacteria, including M. tuberculosis, are surrounded by a loosely attached capsule that is mainly composed of proteins and polysaccharides. Although the chemical composition of the capsule is relatively well studied, its biological function is only poorly understood. The aim of this study was to further assess the functional role of the mycobacterial capsule by identifying host receptors that recognize its constituents. We focused on alpha-glucan, which is the dominant capsular polysaccharide. Here we demonstrate that M. tuberculosis alpha-glucan is a novel ligand for the C-type lectin DC-SIGN (dendritic cell-specific ICAM-3-grabbing nonintegrin). By using related glycogen structures, we show that recognition of alpha-glucans by DC-SIGN is a general feature and that the interaction is mediated by internal glucosyl residues. As for mannose-capped lipoarabinomannan, an abundant mycobacterial cell wall-associated glycolipid, binding of alpha-glucan to DC-SIGN stimulated the production of immunosuppressive IL-10 by LPS-activated monocyte-derived dendritic cells. By using specific inhibitors, we show that this IL-10 induction was DC-SIGN-dependent and also required acetylation of NF-kappa B. Finally, we demonstrate that purified M. tuberculosis alpha-glucan, in contrast to what has been reported for fungal alpha-glucan, was unable to activate TLR2. The Journal of Immunology, 2009, 183: 5221-5231.