Immune Mechanisms of Severe RSV Disease- T Cell and Antibody Responses

描述(申请人提供)：呼吸道合胞病毒(RSV)会导致老年人严重疾病。老年人严重疾病的发病机制可能是多因素的，但衰老免疫反应的失调是了解疾病严重程度的核心。与其他病毒不同，RSV有类型和类型2反应的证据。Typel的反应包括IFNG和IL-12，它们在病毒清除中起重要作用。2型反应包括IL-4、IL-5和IL-10的分泌，在抗寄生虫反应、过敏反应和旺盛的抗体产生中起重要作用。我们最近证明在活动性感染期间RSV特异性的IL-5(类型2)反应与青年和中年人的症状严重程度相关。我们认为RSV-IL-5应答将在老年RSV疾病严重程度中发挥重要作用。与年轻人相比，RSV特异性抗体对感染的反应更强。我们建议研究在RSV感染的老年人中，2型细胞因子和强烈的抗体反应之间的作用和潜在联系。我们研究的目的是为预防和治疗老年人严重的呼吸道合胞病毒疾病提供见解。

DESCRIPTION (provided by applicant): Respiratory Syncytial Virus (RSV) causes severe disease in the elderly. The pathogenesis of severe disease in the elderly is probably multi-factorial but the dysregulation of the aging immune response is central to understanding disease severity. Unlike other viruses, RSV has evidence of typel and type2 responses. Typel responses include IFNg and IL-12 which are important in viral clearance. Type2 responses include IL-4, IL-5, and IL-10 secretion and are important in anti-parasitic responses, allergy and vigorous antibody production. We recently demonstrate that RSV-specific IL-5 (type2) responses during active infection correlate with symptom severity in young and middle-aged adults. We believe that RSV-IL-5 responses will play an important role in RSV disease severity in the elderly. RSV-specific antibody responses to infection are increased compared to young adults. We propose to study the role as well as the potential links between type2 cytokines and vigorous antibody responses in the elderly during RSV infection. The goal of our studies is to provide insights in prevention and treatment of severe RSV disease in the elderly.