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

先天免疫防御在识别和控制病毒感染中起着重要作用。这个系统的一个重要组成部分是浆细胞样树突状细胞(PDC)，最近被确认为血液中I型干扰素的主要制造者。我们的结果表明，不是HIV本身，而是HIV感染的细胞对PDC的干扰素的产生、成熟和迁移具有重要的诱导作用。这一反应似乎是通过特定的表面受体、内吞过程和Toll样受体的信号转导来识别感染病毒的细胞。根据过去资助期间芯片分析的结果，这些分子机制将从三个方面进行评估：(I)哪些病毒决定因素负责干扰素诱导和HIV致病，(Ii)Toll样受体和细胞内信号转导如何参与PDC的成熟和迁移，以及(Iii)病毒感染细胞上表达的哪些细胞分子启动信号级联反应。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。

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.