Influence of maternal immunity on the response of the newborn to RSV infection

描述(申请人提供)：哮喘在呼吸道感染期间加重，这可能有助于其维持和发展。目前的治疗方法无法逆转这一过程，在没有明确病因的情况下，目前的干预措施无法预防哮喘的发展。然而，大多数哮喘患者可以追溯到他们疾病的起源，即早期喘息，可以追溯到生命的头2-3年。由呼吸道合胞病毒(RSV)感染引起的毛细支气管炎发作后，可能会较早出现喘息。呼吸道合胞病毒毛细支气管炎主要发生在出生后的头几个月，当时新生儿的免疫系统仍不成熟，偏向TH2，缺乏对病毒的先前经验。显然，这种新生儿的缺陷可以通过母源因子来弥补。该项目侧重于母体免疫状态所产生的产前到出生后早期的因素，这些因素可能决定新生儿RSV感染后代的结局。拟议的研究将在小鼠模型中进行，该模型已被验证，以揭示母体免疫对新生儿对RSV感染的反应的影响。具体目标是：1-确定母体免疫在新生儿对新生儿RSV感染反应中的影响。研究旨在描绘新生儿反应的这些方面(S)，以确定反应的哪个组成部分受到过敏和非过敏母亲以及呼吸道合胞病毒免疫和非免疫母亲的影响。2-阐明母体免疫影响新生儿对RSV感染反应的潜在机制。研究将确定母体免疫的影响是如何调节的，以及它如何有助于塑造新生儿对RSV感染的反应。3-确定母体免疫是否影响新生儿对新生儿RSV感染后接触变应原的反应。呼吸道合胞病毒感染可增强变应原介导的呼吸道功能障碍。研究将确定母体免疫是否以及如何通过影响新生儿对RSV的反应来调节对随后的过敏原暴露的反应。该项目将确定母体免疫与患呼吸道合胞病毒毛细支气管炎的风险以及相关的子代长期后遗症之间的关键和潜在的可延展性联系。从长远来看，这个项目将提高我们对感染在哮喘中的作用的理解。了解这些感染何时以及如何促成哮喘和过敏性呼吸道疾病的发病机制，是开发有效的预防或治愈疾病的治疗方法的先决条件。

DESCRIPTION (provided by applicant): Asthma exacerbates during respiratory infection, which may contribute to its maintenance and progression. Current therapies fail to reverse this process, and development of asthma cannot be prevented with current interventions in the absence of clear delineation of the etiology. However, most asthma patients can trace the origin of their disease, the early onset of wheezing, to the first 2-3 years of life. Wheezing may develop earlier after an episode of bronchiolitis, caused by infection of the lower respiratory tract with respiratory syncytial virus (RSV). RSV bronchiolitis occurs mostly during the first few months of life, when the newborn's immune system is still immature, TH2-biased and lacks prior experience to the virus. Apparently, this neonatal deficiency can be compensated for by maternally derived factors. This project focuses on antenatal to early postnatal factors derived from the state of maternal immunity that may determine the outcome of neonatal RSV infection in the offspring. The proposed studies will be conducted in a mouse model, which has been validated to reveal the influences of maternal immunity on the response of the neonate to RSV infection. The specific aims are: 1- To define the influence of maternal immunity in the response of the newborn to neonatal RSV infection. Studies are designed to delineate those aspects of the neonatal response(s) to identify which component of the response is influenced by maternal immunity from allergic and non-allergic, and RSV-immune and non-immune mothers. 2- To elucidate the underlying mechanisms whereby maternal immunity influences the response of the newborn to RSV infection. Studies will determine how the influence of maternal immunity is mediated and how it contributes to shaping the response of the newborn to RSV infection. 3- To determine if maternal immunity influences the response of the newborn to allergen exposure following neonatal RSV infection. RSV infection enhances allergen-mediated airway dysfunction. Studies will determine if and how maternal immunity, by influencing the response to RSV in the newborn, may modulate the response to subsequent allergen exposure. This project will define a critical and potentially malleable link between maternal immunity and the risk of development of RSV bronchiolitis and associated long-term sequelae in the offspring. In the long-term, this project will improve our understanding of the role of infection in asthma. Understanding when and how these infections contribute to the pathogenesis of asthma and allergic airway disease is prerequisite to the development of effective therapies to prevent or cure the disease.