Plasmacytoid dendritic cell (PDC) innate immune defense against human immunodeficiency virus type 1 (HIV-1)

浆细胞样树突状细胞 (PDC) 针对人类免疫缺陷病毒 1 型 (HIV-1) 的先天免疫防御

• 批准号: 33462323
• 负责人: Professorin Dr. Barbara Schmidt
• 金额: --
• 依托单位: Institut für Mikrobiologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/33462323?language=en
• 关键词: Plasmacytoid; dendritic; cell; PDC; innate

The innate immune defense plays an important role in the recognition and control of viral infections. A crucial component of this system are the plasmacytoid dendritic cells (PDC), which have recently been identified as major producers of type I interferons in the blood. Our results show that not HIV itself, but HIV-infected cells are important for the induction of interferon production, maturation, and migration of PDC. This response seems to be mediated by the recognition of virus-infected cells via specific surface receptors, endocytotic processes and signal transduction via Toll-like receptors. Based on findings obtained by chip analysis during the past funding period, these molecular mechanisms will be evaluated in three respects: (i) which viral determinants are responsible for interferon induction and HIV pathogenicity, (ii) how Toll-like receptors and intracellular signal transduction are involved in PDC maturation and migration, and (iii) which cellular molecule expressed on virus-infected cells initiates the signaling cascade. The results of this project will elucidate the role of PDC and mature dendritic cells for the control of HIV infection and HIV pathogenesis. In addition, targets will be identified which will offer new therapeutic approaches for modifying innate immune responses.

先天免疫防御在识别和控制病毒感染中发挥着重要作用。该系统的一个重要组成部分是浆细胞样树突状细胞（PDC），最近被确定为血液中 I 型干扰素的主要产生者。我们的结果表明，不是 HIV 本身，而是 HIV 感染的细胞对于诱导 PDC 的干扰素产生、成熟和迁移很重要。这种反应似乎是通过特定表面受体、内吞过程和 Toll 样受体的信号转导来识别病毒感染的细胞来介导的。根据过去资助期间芯片分析获得的结果，这些分子机制将从三个方面进行评估：（i）哪些病毒决定簇负责干扰素诱导和HIV致病性，（ii）Toll样受体和细胞内信号转导如何参与PDC成熟和迁移，以及（iii）病毒感染细胞上表达的哪种细胞分子启动信号传导 级联。该项目的结果将阐明 PDC 和成熟树突状细胞在控制 HIV 感染和 HIV 发病机制中的作用。此外，还将确定靶点，为改变先天免疫反应提供新的治疗方法。