The scavenger receptors SRA-1 and SREC-I cooperate with TLR2 in the recognition of the hepatitis C virus non-structural protein 3 by dendritic cells
The scavenger receptors SRA-1 and SREC-I cooperate with TLR2 in the recognition of the hepatitis C virus non-structural protein 3 by dendritic cells
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DOI：
10.1016/j.jhep.2009.11.031
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发表时间：
2010-05-01
影响因子：
25.7
通讯作者：
Jeannin, Pascale
中科院分区：
文献类型：
--
作者：
Beauvillain, Celine;Meloni, Francesca;Jeannin, Pascale
背景和目的：丙型肝炎病毒 NS3 蛋白以不依赖于 TLR2 的方式被骨髓细胞摄取，并通过 TLR2 激活骨髓细胞。本研究旨在鉴定参与骨髓细胞摄取 NS3 的内吞受体及其与 TLR2 的关系。方法：使用抑制剂和转染细胞来鉴定骨髓细胞表达的 NS3 结合受体的性质。使用抑制剂、来自 TLR2(-/-) 小鼠的细胞和共聚焦显微镜评估了清道夫受体 (SR) 和 TLR2 在 NS3 介导的骨髓细胞激活中的合作。使用 NS3 特异性人 T 细胞克隆在体外评估 SR 在 NS3 交叉呈递中的参与。结果：我们观察到 SR 是 NS3 在骨髓细胞上的主要结合结构，并确定 SR SRA-1 和 SREC-I 是 NS3 的内吞受体。此外，SR 和 TLR2 在 NS3 诱导的骨髓细胞激活中协同作用。结论：这项研究强调了 SR 在 NS3 摄取和交叉呈递中的核心作用，并证明了信号传导和内吞先天受体在 NS3 识别中紧密协调的合作。 (C) 2010 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Backgrounds & Aims: The hepatitis C virus NS3 protein is taken up by myeloid cells in a TLR2-independent manner and activates myeloid cells via TLR2. This study aimed to identify the endocytic receptor(s) involved in the uptake of NS3 by myeloid cells and its relation with TLR2.Methods: Inhibitors and transfected cells were used to identify the nature of the NS3-binding receptors expressed by myeloid cells. The cooperation between scavenger receptors (SRs) and TLR2 in the NS3-mediated activation of myeloid cells was evaluated using inhibitors, cells from TLR2(-/-) mice, and confocal microscopy. The involvement of SRs in NS3 cross-presentation was evaluated in vitro using an NS3-specific human T-cell clone.Results: We observed that SRs are the main binding structures for NS3 on myeloid cells and identified the SRs SRA-1 and SREC-I as endocytic receptors for NS3. Moreover, both SRs and TLR2 cooperate in NS3-induced myeloid cell activation.Conclusion: This study highlights a central role for SRs in NS3 uptake and cross-presentation, and demonstrates a tightly orchestrated cooperation between signalling and endocytic innate receptors in NS3 recognition. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.