Pattern recognition by TREM-2: Binding of anionic ligands
Pattern recognition by TREM-2: Binding of anionic ligands
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DOI：
10.4049/jimmunol.171.2.594
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Seaman, WE
中科院分区：
文献类型：
--
作者：
Daws, MR;Sullam, PM;Seaman, WE
我们最近描述了髓系细胞表达的鼠触发受体（TREM）2的克隆，TREM 2是髓系细胞表达的单IG结构域DNAX衔接蛋白12相关受体。在这项研究中，我们描述了细菌和哺乳动物细胞上TREM-2的配体的鉴定。首先，通过使用TREM-2A/IgG 1-Fc融合蛋白，我们证明了与许多革兰氏阴性和革兰氏阳性细菌以及酵母的特异性结合。此外，我们发现荧光标记的大肠杆菌和金黄色葡萄球菌特异性结合TREM-2转染细胞。TREM-2A/IG融合蛋白与E.大肠杆菌能被细菌产物LPS、脂磷壁酸和肽聚糖抑制。此外，结合可以被许多其他阴离子碳水化合物分子抑制，包括硫酸葡聚糖，这表明配体识别部分基于电荷。使用灵敏的报告基因测定，我们证明了细菌和硫酸葡聚糖对TREM-2A/CD 3 zeta嵌合受体的激活。最后，我们证明了TREM-2A/IG融合体与一系列人星形细胞瘤细胞系的结合，但不与多种其他细胞系结合。与星形细胞瘤的结合，如与细菌的结合，被阴离子细菌产物抑制，这表明类似的基于电荷的配体识别方法或重叠的结合位点用于识别自身和病原体表达的配体。
We recently described the cloning of murine triggering receptor expressed by myeloid cells (TREM) 2, a single Ig domain DNAX adaptor protein 12-associated receptor expressed by cells of the myeloid lineage. In this study, we describe the identification of ligands for TREM-2 on both bacteria and mammalian cells. First, by using a TREM-2A/IgG1-Fc fusion protein, we demonstrate specific binding to a number of Gram-negative and Gram-positive bacteria and to yeast. Furthermore, we show that fluorescently labeled Escherichia coli and Staphylococcus aureus bind specifically to TREM-2-transfected cells. The binding of TREM-2A/Ig fusion protein to E. coli can be inhibited by the bacterial products LPS, lipoteichoic acid, and peptidoglycan. Additionally, binding can be inhibited by a number of other anionic carbohydrate molecules, including dextran sulfate, suggesting that ligand recognition is based partly on charge. Using a sensitive reporter assay, we demonstrate activation of a TREM-2A/CD3zeta chimeric receptor by both bacteria and dextran sulfate. Finally, we demonstrate binding of TREM-2A/Ig fusion to a series of human astrocytoma lines but not to a variety of other cell lines. The binding to astrocytomas, like binding to bacteria, is inhibited by anionic bacterial products, suggesting either a similar charge-based ligand recognition method or overlapping binding sites for recognition of self- and pathogen-expressed ligands.