DENDRITIC CELLS, RSV AND INFLUENZA INFECTION IN CHILDREN

儿童树突状细胞、RSV 和流感感染

• 批准号: 6884108
• 负责人: Octavio Ramilo
• 金额: $ 23.4万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-15 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6884108
• 关键词: T lymphocyte; antigen presentation; cell cell interaction; cell differentiation; cell line; cell proliferation; clinical research; confocal scanning microscopy; cytokine; dendritic cells; flow cytometry; helper T lymphocyte; host organism interaction; human subject; immune response; infant human (0-1 year); influenza; longitudinal human study; patient oriented research; pediatrics; phenotype; preschool child (1-5); respiratory infections; respiratory syncytial virus; tissue /cell culture; virus infection mechanism

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is the principal etiologic agent of bronchiolitis and viral pneumonia in infants and young children worldwide. Influenza viruses also contribute to significant number of hospitalizations among children. While the clinical manifestations are similar, there are remarkable differences in terms of their immune responses. In a simplified comparison, RSV does not induce protective immunity, there is no available vaccine, and it is associated with recurrent wheezing. In contrast, influenza does induce a more effective protective immune response, vaccines are quite effective, and it is not associated with long-term wheezing. This provides an ideal setting for a comparative analysis of the immune responses of children with these two viral infections. Dendritic cells (DCs) constitute a complex system of cells with a unique ability to induce primary immune responses. In addition, emerging evidence indicates that DCs control cytokine production by T cells and regulate the Th1/Th2 balance of the immune responses. Numerous studies have demonstrated the importance of the interaction between viruses and different DCs subsets and how that initial interaction influences the development of the subsequent immune responses. Although to date, not much is known about the interaction between DCs and RSV, our preliminary results suggest a direct participation of DCs in the immune response to RSV infection in children. Our hypothesis is that RSV and influenza virus target DC differentially leading to different immune responses, mostly deleterious in case of RSV and protective in case of influenza. We will begin to address this hypothesis in the following specific aims: 1. To determine how RSV and influenza infection affect human DC subsets in vivo, and 2. To determine how RSV and influenza infection affect human DC subsets in vitro, These studies will permit us to define the nature of the DC subset(s) that constitute the target of RSV and influenza infection in children, and begin to identify the mechanisms implicated in the interaction between these respiratory viruses and DCs.

描述（由申请方提供）：呼吸道合胞病毒（RSV）是全球婴幼儿毛细支气管炎和病毒性肺炎的主要病原体。 流感病毒也是导致大量儿童住院的原因之一。 虽然临床表现相似，但在免疫反应方面存在显着差异。 在一个简单的比较中，RSV不诱导保护性免疫，没有可用的疫苗，并且它与反复喘息有关。 相比之下，流感确实会诱导更有效的保护性免疫反应，疫苗相当有效，并且与长期喘息无关。 这为比较分析这两种病毒感染儿童的免疫反应提供了理想的环境。 树突状细胞（Dendritic cells，DC）是一种复杂的细胞系统，具有诱导原发性免疫应答的独特能力。 此外，新出现的证据表明，DC控制T细胞的细胞因子产生并调节免疫应答的Th 1/Th 2平衡。 许多研究已经证明了病毒与不同DC亚群之间相互作用的重要性，以及这种初始相互作用如何影响随后免疫应答的发展。 尽管迄今为止，对DC和RSV之间的相互作用知之甚少，但我们的初步结果表明，DC直接参与了儿童对RSV感染的免疫应答。 我们的假设是RSV和流感病毒不同地靶向DC，导致不同的免疫应答，在RSV的情况下主要是有害的，而在流感的情况下是保护性的。 我们将开始解决这个假设在以下具体目标：1。确定RSV和流感病毒感染如何影响体内人DC亚群，以及2.为了确定RSV和流感病毒感染如何影响体外人DC亚群，这些研究将使我们能够定义构成RSV和流感病毒感染儿童靶点的DC亚群的性质，并开始鉴定这些呼吸道病毒与DC之间相互作用的机制。