Alteration of Human Dendritic Cell Subsets by RSV

描述(申请人提供)：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，因此在一生中反复发生RSV感染。除了急性呼吸道合胞病毒感染引起的相当大的发病率外，许多研究已经描述了婴儿期呼吸道合胞病毒毛细支气管炎与晚年肺功能异常之间的强烈关联。对RSV感染的免疫反应的夸大被认为在这些长期肺部异常的发展中起着重要作用。然而，尽管经过了几十年的研究，我们对RSV诱导的免疫反应的了解仍然有限。这项建议的目的是在人类树突状细胞(DC)的背景下研究RSV对免疫系统的影响，因为这些细胞具有独特的诱导初级免疫反应的能力，从而连接天然免疫系统和获得性免疫系统。该项目的中心假设是，RSV通过靶向浆细胞样树突状细胞，使免疫反应向2型炎症反应倾斜。本文建议的研究将开始确定RSV和DC之间相互作用的机制，以及这些相互作用如何影响T细胞反应的建立。我们相信，这些研究最终可能有助于开发旨在预防RSV感染的免疫调节策略。 应聘者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，并使她能够发展成为一名独立调查人员。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病理机制，重点是DC在这种关系中的作用。为了帮助实现这一目标，研究提案呼吁获得新的科学技术和智力技能，同时同时调查一个及时的研究项目，即呼吸道合胞病毒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，提供了可用的实验室设施/设备和致力于指导候选人的经验丰富、成功的教职员工。这一奖项将促进候选人转变为一名独立的、学术的内科科学家。

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.