Mannan binding lectin attenuates double-stranded RNA-mediated TLR3 activation and innate immunity
Mannan binding lectin attenuates double-stranded RNA-mediated TLR3 activation and innate immunity
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甘露聚糖结合凝集素减弱双链 RNA 介导的 TLR3 激活和先天免疫
DOI：
10.1016/j.febslet.2014.01.064
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发表时间：
2014-03-18
期刊：
影响因子：
3.5
通讯作者：
Zuo, Daming
中科院分区：
文献类型：
--
作者：
Liu, Hongzhi;Zhou, Jia;Zuo, Daming
甘露聚糖结合凝集素 (MBL) 作为模式识别分子 (PRM) 发挥作用，能够启动补体激活。在这里，我们将 MBL 的一个以前未被识别的属性描述为一种双链 RNA (dsRNA) 结合蛋白，能够改变 Toll 样受体 3 (TLR3) 的激活。 MBL 与 Poly(I:C) 相互作用并抑制 Poly(I:C) 诱导的 TLR3 通路激活和随后的细胞因子产生。此外，MBL 直接与 TLR3 结合。令人惊讶的是，破坏 MBL 和补体受体 1 (CR1) 之间的相互作用或抑制 MBL 向吞噬体的运输可逆转 MBL 限制的 TLR3 激活。我们证明了 MBL 引导配体细胞内定位的重要性，强调了了解细胞内与 MBL 或其他 PRM 复合的 TLR 激动剂在免疫防御中的动态的重要性。蛋白质相互作用的结构化摘要::TLR3 通过抗诱饵免疫共沉淀与 MBL 发生物理相互作用（查看相互作用）TLR3 和 MBL 通过荧光显微镜共定位（查看相互作用）(C) 2014 年欧洲生化协会联合会。由 Elsevier B.V 出版。保留所有权利。
Mannan binding lectin (MBL) functions as a pattern recognition molecule (PRM) which is able to initiate complement activation. Here, we characterize a previously unrecognized attribute of MBL as a double-stranded RNA (dsRNA) binding protein capable of modifying Toll like receptor 3 (TLR3) activation. MBL interacts with poly(I: C) and suppresses poly(I: C)-induced activation of TLR3 pathways and subsequent cytokine production. In addition, MBL binds to TLR3 directly. Surprisingly, disrupting the interaction between MBL and complement receptor 1 (CR1) or restraining the traffic of MBL to phagosome reversed the MBL limited TLR3 activation. We demonstrate the importance of MBL guided ligands intracellular localization, emphasizing the significance of understanding the dynamics of TLR agonists complexed with MBL or other PRMs inside the cell in immune defense.Structured summary of protein interactions::TLR3 physically interacts with MBL by anti bait coimmunoprecipitation (View interaction)TLR3 and MBL colocalize by fluorescence microscopy (View interaction) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.