Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily
Combinational recognition of bacterial lipoproteins and peptidoglycan by chicken Toll-like receptor 2 subfamily
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DOI：
10.1016/j.dci.2007.05.003
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发表时间：
2008-01-01
影响因子：
2.9
通讯作者：
Seya, Tsukasa
中科院分区：
文献类型：
--
作者：
Higuchi, Megumi;Matsuo, Aya;Seya, Tsukasa
人Toll样受体2(TLR2)亚家族识别细菌脂蛋白(BLP)和肽聚糖(PGN)。根据基因组信息，鸡除了TLRs3、4、5和7外，还有TLRs1和2的结构同源物。鸡还有两个TLRs，TLR15和TLR21，这是人类缺乏的同源物。鸡(Ch)TLR1和2基因分别重复编码TLR2亚家族的四种不同蛋白：chTLR1-1、1-2、2-1和2-2。在这里，我们研究了这些鸡TLR2亚家族蛋白的功能图谱。通过使用HEK293细胞进行的NF-kappa B报告分析，我们发现chTLR2-1和chTLR1-2协同信号显示PGN的存在。ChTLR2-1和chTLR1-2的组合也最有效地识别二酰化BLP，巨噬细胞激活脂肽2 kDa(Malp-2)，而chTLR2-1和chTLR1-1的组合不能识别Malp-2。然而，所有的组合都识别三酰化的BLP，Pamm3。与这些结果一致的是，刺激人TLR2的分枝杆菌制剂、卡介苗细胞壁和禽分枝杆菌的细胞裂解物，在表达chTLR2-1和1-2的细胞中诱导了NF-kappa B的激活，在较小程度上诱导了含有chTLR2-2的细胞和chTLR1的激活。值得注意的是，单独表达这两种受体中的任何一种都不能激活核因子-kappa B的报告。这些chTLRs可能具有与人类TLR2亚家族相同的组合功能特征。共聚焦和免疫共沉淀分析表明，人细胞转染体以物理分子结合的方式聚集在细胞表面，导致它们全部合并和共沉淀。这些结果表明，chTLR2亚家族成员通过组合事件区分他们的配体。(C)2007爱思唯尔有限公司。保留所有权利。
Human Toll-like receptor 2 (TLR2) subfamily recognizes bacterial lipoproteins (BLP) and peptidoglycan (PGN). According to the genome information, chicken has structural orthologs of TLRs1 and 2, in addition to TLRs3, 4, 5 and 7. Chicken has two additional TLRs, TLR15 and TLR21, whose orthologs human lacks. The chicken (ch)TLR1 and 2 genes are individually duplicated to encode for four different proteins, chTLR1-1, 1-2, 2-1 and 2-2, of the TLR2 subfamily. Here we investigated the functional profile of these TLR2 subfamily proteins of chicken. By NF-kappa B reporter assay using HEK293 cells, we found that chTLR2-1 and chTLR1-2 cooperatively signal the presence of PGN. A combination of chTLR2-1 and chTLR1-2 also most efficiently recognized diacylated BLP, macrophage-activating lipopeptide 2 kDa (Malp-2), while the combination of chTLR2-1 and chTLR1-1 failed to recognize Malp-2. All combinations, however, recognized triacylated BLP, Pamm3. Consistent with these results, human TLR2-stimulating mycobacteria preparations, BCG-cell wall and cell lysate of Mycobacterium avium, induced activation of NF-kappa B in cells expressing chTLR2-1 and 1-2 and to lesser extents, cells with chTLR2-2 and either of chTLR1. Strikingly, expression of either of these alone did not activate the reporter for NF-kappa B. These chTLRs are likely to have the combination functional feature as in the human TLR2 subfamily. Confocal and immunoprecipitation analyses of human cell transfectants showed that they cluster on the cell surface by a physical molecular association, causing all of them to merge and coprecipitate. These results suggest that chTLR2 subfamily members discriminate between their ligands by combinational events. (C) 2007 Elsevier Ltd. All rights reserved.