Molecular Immunopathogenesis of DHF/DSS

该项目的长期目标是定义 确定登革病毒(DV)感染的结局。大量信息支持 严重登革热的免疫发病机制模型；然而，关于 疾病的主要决定因素。DV与宿主天然免疫和获得性免疫的相互作用 反应是高度复杂的，可以导致促炎、抗炎、 和/或血管活性细胞因子。本项目旨在了解以下方面的贡献 免疫反应的个体成分对不同的临床疾病表现。这些 通过确定关键的免疫学相关性，研究结果将对疫苗开发具有重要意义。 疫苗诱导的保护，而不是针对随后暴露于DV的免疫病理学。 该项目的具体目标是： 1.为了确定对dv感染的细胞反应的病毒和固有宿主决定因素， 树突状细胞(DC)细胞因子对不同DV毒株的应答 疾病严重程度和DC反应与宿主基因型别的关系； 2.确定在急性DV感染中导致临床疾病的免疫学机制， 通过测定DV特异性B细胞和T细胞的活化和扩增动力学； 3.为了确定对四价DV免疫应答的免疫学相关性， 确定预先存在的DV特异性免疫与免疫应答之间的关联 疫苗接种及疫苗诱导的DV特异性免疫与临床结局之间的关系 (不良事件、保护和突破性DV感染)。 登革热是一种重要的热带蚊媒病毒疾病，会导致休克。 身体的免疫反应。我们将研究宿主免疫系统的不同部分是如何反应的 感染登革热病毒以了解病毒感染是如何致病的。这项研究将 帮助指导登革热疫苗和新疗法的开发。

The long-term objective of this project is to define the immunological mechanisms that determine the outcome of dengue virus (DV) infection. A large body of information supports the model of immunopathogenesis of severe dengue disease; however, open questions remain about the principal determinants of disease. DV interaction with host innate and adaptive immunity responses is highly complex, and can result in the production of pro-inflammatory, antiinflammatory, and/or vasoactive cytokines. This Project seeks to understand the contribution of individual components of the immune response to different clinical disease manifestations. These findings will be important for vaccine development, by identifying the key immunologic correlates of vaccine-induced protection as opposed to immunopathology on subsequent exposure to DV. The Specific Aims of this Project are: 1. to define the viral and innate host determinants of the cellular response to DV infection, by determining the dendritic cell (DC) cytokine response to DV strains associated with different disease severity and the association of DC responses with host genotypes; 2. to define the immunological mechanisms contributing to clinical disease in acute DV infection, by determining the kinetics of activation and expansion of DV-specific B cells and T cells; 3. to define immunological correlates of the response to tetravalent DV immunization, by determining the associations between pre-existing DV-specific immunity and the response to vaccination and between the vaccine-induced DV-specific immunity and clinical outcome (adverse events, protection, and breakthrough DV infections). Dengue is an important tropical mosquito-borne viral disease that causes shock as a result of the body's immune response. We will study how different parts of the host immune system react to infection with dengue virus to understand how virus infection causes disease. This research will help guide the development of vaccines and new treatments for dengue.