DENDRITIC CELLS, RSV AND INFLUENZA INFECTION IN CHILDREN

描述(申请人提供)：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。流感病毒还导致大量儿童住院。虽然临床表现相似，但在免疫反应方面存在显著差异。在一个简化的比较中，RSV不会诱导保护性免疫，也没有可用的疫苗，而且它与反复喘息有关。相比之下，流感确实诱导了更有效的保护性免疫反应，疫苗相当有效，而且它与长期喘息无关。这为比较分析患有这两种病毒感染的儿童的免疫反应提供了理想的环境。 树突状细胞(DC)构成了一个复杂的细胞系统，具有诱导初始免疫反应的独特能力。此外，新的证据表明，DC控制T细胞产生细胞因子，调节免疫反应的Th1/Th2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，以及这种最初的相互作用如何影响后续免疫反应的发展。虽然到目前为止，关于DC和RSV之间的相互作用还不是很清楚，但我们的初步结果表明，DC直接参与了儿童对RSV感染的免疫反应。 我们的假设是，RSV和流感病毒针对DC的不同导致不同的免疫反应，在RSV情况下主要是有害的，在流感情况下是保护的。1.确定呼吸道合胞病毒和流感感染如何在体内影响人类DC亚群；2.为了确定呼吸道合胞病毒和流感感染在体外如何影响人类DC亚群，这些研究将使我们能够定义构成呼吸道合胞病毒和流感在儿童中感染靶点的DC亚群(S)的性质，并开始识别这些呼吸道病毒和DC之间相互作用的机制。

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.