Molecular mechanism whereby Type I interferon is induced in host immune cells by measles virus infection : possible involvement of Toll-like receptors (TLRs)

麻疹病毒感染在宿主免疫细胞中诱导 I 型干扰素的分子机制：可能涉及 Toll 样受体 (TLR)

• 批准号: 15390154
• 负责人: SEYA Tsukasa
• 金额: $ 8.38万
• 依托单位: HOKKAIDO UNIVERSITY (2004-2005)Research Institute, Osaka Medical Center for Cancer and Cardiovascular Disaeses (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390154/
• 关键词: Measles virus; TLR3; dendritic cell; dsRNA; CD46; SLAM; IRE-3; IFN-β; 麻疹ウィルス; TLR2; irf-3

TLR3 fosters the induction of type I interferon (IFN) in myeloid dendritic cells (mDCs) in response to exogenously-added dsRNA. Recently, CARD-helicase family proteins, RIG-I and MDA5, are found to be involved in recognition of cytoplasmic dsRNA, presumably of viral origin. Thus, through these sensor molecules virus infection culminates in IFN response. In this study, we have identified the adapter molecule of TLR3 that induces IFN-β and named TICAM-1 (also called Trif). We established CD46/CD150 double TG mice and performed measles infection studies using the TG mice. The TG mice were not measles-sensitive until the IFNAR gene was simultaneously disrupted in addition to the TG. CD11c-positive mDCs were engaged in establishing the initial infection with measles virus. What are the role of TLR3 in mDCs during measles infection and their relation to immune suppression are currently under investigation.

TLR 3促进髓样树突状细胞（mDC）中I型干扰素（IFN）的诱导以响应外源添加的dsRNA。最近，CARD-解旋酶家族蛋白，RIG-I和MDA 5，被发现参与识别细胞质dsRNA，推测是病毒来源的。因此，通过这些传感器分子，病毒感染在IFN应答中达到高潮。在这项研究中，我们已经鉴定了诱导IFN-β的TLR 3的接头分子，并命名为TICAM-1（也称为Trif）。我们建立了CD 46/CD 150双TG小鼠，并使用TG小鼠进行麻疹感染研究。TG小鼠对麻疹不敏感，直到IFNAR基因与TG同时被破坏。CD 11 c阳性mDC参与麻疹病毒初始感染的建立。目前正在研究麻疹感染期间TLR 3在mDC中的作用及其与免疫抑制的关系。

项目成果

CR3/CR4 補体receptors

CR3/CR4补体受体

• 发表时间: 2005
• 期刊: 血液・尿化学検査・免疫学的検査(日本臨床) 48
• 作者: 舟見健児;瀬谷司
• 通讯作者: 瀬谷司

Differential maturation of dendritic cells by TLR adapters : application to immunotherapy.

TLR 接头使树突状细胞分化成熟：在免疫治疗中的应用。

• 发表时间: 2004
• 期刊: Princess Takamatsu Symposia 34
• 作者: Seya;T. et al.
• 通讯作者: T. et al.

Multifunctional feature of Toll-like receptor 3 cytoplasmic tail that regulates receptor localization and signaling.

Toll 样受体 3 胞质尾部的多功能特征可调节受体定位和信号传导。

• 发表时间: 2004
• 期刊: Int.Immunol. 16
• 作者: Funami;K.;Seya et al.
• 通讯作者: Seya et al.

抗腫瘍免疫における自然免疫系の役割

先天免疫系统在抗肿瘤免疫中的作用

• 发表时间: 2004
• 期刊: 血液・免疫・腫瘍 9
• 作者: 瀬谷司;松本美佐子;赤澤隆
• 通讯作者: 赤澤隆

Dendritic cell maturation induced by muramyl dipeptide (MDP) derivatives : monoacylated MDP confers TLR2/TLR4 activation.

胞壁酰二肽 (MDP) 衍生物诱导树突状细胞成熟：单酰化 MDP 赋予 TLR2/TLR4 激活。

• 发表时间: 2005
• 期刊: J.Immunol 174・11
• 作者: Uehara;A;Y.Fujimoto;A.Uehara;H.Tokimoto;J.Uehori
• 通讯作者: J.Uehori