Plasmacytoid Dendritic Cells and Infected Cells Form an Interferogenic Synapse Required for Antiviral Responses
Plasmacytoid Dendritic Cells and Infected Cells Form an Interferogenic Synapse Required for Antiviral Responses
复制标题
DOI：
10.1016/j.chom.2019.03.005
复制
发表时间：
2019-05-08
影响因子：
30.3
通讯作者：
Dreux, Marlene
中科院分区：
文献类型：
--
作者：
Assil, Sonia;Coleon, Severin;Dreux, Marlene
I型干扰素（IFN-I）对于抗病毒防御是关键的，并且浆细胞样树突状细胞（pDC）是病毒感染期间IFN-I的主要来源。pDC介导的抗病毒应答在与感染细胞物理接触时被刺激，在此期间免疫刺激性病毒RNA被转移到pDC，导致通过核酸传感器TLR 7产生IFN。使用登革热，丙型肝炎和寨卡病毒，我们证明了pDC与感染细胞的接触部位是一个专门的平台，我们称之为干扰素突触，它使病毒RNA转移和抗病毒反应成为可能。该突触通过aLb 2整联蛋白-ICAM-1粘附复合物和肌动蛋白网络和内吞机制的募集形成。pDC中的TLR 7信号传导促进干扰原性突触建立并提供前馈调节，维持pDC与感染细胞的接触。这种干扰源性突触可允许pDC扫描受感染的细胞并局部分泌IFN-1，从而限制潜在的有害反应。
Type I interferon (IFN-I) is critical for antiviral defense, and plasmacytoid dendritic cells (pDCs) are a predominant source of IFN-I during virus infection. pDC-mediated antiviral responses are stimulated upon physical contact with infected cells, during which immunostimulatory viral RNA is transferred to pDCs, leading to IFN production via the nucleic acid sensor TLR7. Using dengue, hepatitis C, and Zika viruses, we demonstrate that the contact site of pDCs with infected cells is a specialized platform we term the interferogenic synapse, which enables viral RNA transfer and antiviral responses. This synapse is formed via aLb2 integrin-ICAM-1 adhesion complexes and the recruitment of the actin network and endocytic machinery. TLR7 signaling in pDCs promotes interferogenic synapse establishment and provides feed-forward regulation, sustaining pDC contacts with infected cells. This interferogenic synapse may allow pDCs to scan infected cells and locally secrete IFN-I, thereby confining a potentially deleterious response.