Alteration of Human Dendritic Cell Subsets by RSV

RSV 对人类树突状细胞亚群的改变

• 批准号: 7057313
• 负责人: MICHELLE A GILL
• 金额: $ 11.88万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7057313
• 关键词: Orthomyxoviridae; T lymphocyte; antigen presentation; clinical research; confocal scanning microscopy; cytokine; dendritic cells; flow cytometry; human subject; immune response; inflammation; lymphocyte proliferation; microarray technology; respiratory syncytial virus; tetanus toxoid; tissue /cell culture; virus infection mechanism

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the leading respiratory pathogen in infants and young children worldwide. RSV infection does not induce protective immunity and therefore repeated RSV infections occur throughout life. In addition to the considerable morbidity caused by acute RSV infections, numerous studies have described a strong association between RSV bronchiolitis in infancy and abnormal pulmonary function later in life. Exaggeration of the immune response to RSV infection is thought to play a significant role in the development of these long-term pulmonary abnormalities. Despite decades of research, however, our understanding of the immune responses induced by RSV remains limited. The goal of this proposal is to investigate the effect of RSV on the immune system in the context of human dendritic cells (DCs), since these cells are uniquely capable of inducing primary immune responses and thus bridge the innate and adaptive immune systems. The central hypothesis of this project is that RSV skews immune responses toward Type 2 inflammatory responses via targeting plasmacytoid DCs. The studies proposed herein will begin to define the mechanisms involved in the interaction between RSV and DCs and how these interactions influence the establishment of T cell responses. We believe that these studies may ultimately contribute to the development of immunomodulatory strategies aimed at prevention of RSV infection. The immediate goal of the candidate is to procure further training in basic science investigation to enhance her research skills and allow her to develop a career as an independent investigator. As a career focus, the candidate plans to concentrate on the immunopathogenesis of the host/viral pathogen relationship with an emphasis on the role of DCs in this relationship. To assist in achieving this goal, the research proposal calls for the attainment of new scientific technical and intellectual skills while concurrently investigating a timely research project, the alterations of human dendritic cell subsets by RSV. Both the University of Texas Southwestern Medical Center and the Baylor Institute for Immunology Research provide fertile laboratory environments in terms of available laboratory facilities/equipment and experienced, successful faculty members committed to mentoring the candidate. This award will facilitate the transition of the candidate into an independent, academic physician scientist.

描述（由申请方提供）：呼吸道合胞病毒（RSV）是全球婴幼儿的主要呼吸道病原体。RSV感染不会诱导保护性免疫，因此在整个生命周期中会发生反复RSV感染。除了由急性RSV感染引起的相当大的发病率之外，许多研究已经描述了婴儿期RSV细支气管炎与以后生活中的肺功能异常之间的强关联。对RSV感染的免疫应答的放大被认为在这些长期肺异常的发展中起重要作用。然而，尽管经过数十年的研究，我们对RSV诱导的免疫反应的理解仍然有限。本提案的目的是研究RSV在人树突状细胞（DC）背景下对免疫系统的影响，因为这些细胞独特地能够诱导初次免疫应答，从而桥接先天性和适应性免疫系统。该项目的中心假设是RSV通过靶向浆细胞样DC使免疫应答偏向2型炎症应答。本文提出的研究将开始以确定RSV和DC之间相互作用所涉及的机制以及这些相互作用如何影响T细胞应答的建立。我们相信，这些研究可能最终有助于开发旨在预防RSV感染的免疫调节策略。 候选人的近期目标是获得基础科学调查方面的进一步培训，以提高她的研究技能，并使她能够发展作为独立调查员的职业生涯。作为职业重点，候选人计划专注于宿主/病毒病原体关系的免疫发病机制，重点是DC在这种关系中的作用。为了帮助实现这一目标，该研究提案要求获得新的科学技术和知识技能，同时调查一个及时的研究项目，RSV对人类树突状细胞亚群的改变。德克萨斯大学西南医学中心和贝勒免疫学研究所都提供了肥沃的实验室环境，包括可用的实验室设施/设备以及致力于指导候选人的经验丰富、成功的教职员工。该奖项将促进候选人转变为独立的学术医生科学家。