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

母体免疫力对新生儿RSV感染反应的影响

• 批准号: 8094207
• 负责人: AZZEDDINE DAKHAMA
• 金额: $ 30.88万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-20 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8094207
• 关键词: Allergens; Allergic; Asthma; Breast Feeding; Bronchiolitis; CD4 Positive T Lymphocytes; Cells; Development; Disease; Etiology; Functional disorder; Histopathology; Hypersensitivity; Immune; Immune system; Immunity; Infection; Inflammatory; Influentials; Intervention; Life; Link; Lower Respiratory Tract Infection; Maintenance; Mediating; Mothers; Mus; Nature; Neonatal; Newborn Infant; Outcome; Pathogenesis; Patients; Phase; Phenotype; Pregnancy; Process; Research Design; Research Personnel; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Respiratory physiology; Respiratory syncytial virus; Risk; Role; Shapes; T-Lymphocyte; Time; Viral Load result; Virus; Wheezing; adaptive immunity; allergic airway disease; early onset; effective therapy; experience; improved; mouse model; neonate; offspring; postnatal; prevent; programs; response

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.

描述（由申请人提供）：哮喘在呼吸道感染期间加重，这可能有助于其维持和进展。目前的治疗方法无法逆转这一过程，在缺乏明确病因描述的情况下，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其疾病的起源，即早期发作的喘息，直到生命的前2-3年。由呼吸道合胞病毒（RSV）引起的下呼吸道感染引起的毛细支气管炎发作后，喘息可能更早发生。呼吸道合胞病毒细支气管炎主要发生在出生后的头几个月，此时新生儿的免疫系统尚不成熟，存在th2偏倚，缺乏先前对病毒的经验。显然，这种新生儿缺陷可以通过母体衍生的因素来弥补。该项目侧重于产前至产后早期的因素，这些因素源于母体免疫状态，可能决定后代新生儿呼吸道合胞病毒感染的结果。该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。具体目的是：1-确定母体免疫在新生儿对新生儿呼吸道合胞病毒感染反应中的影响。研究旨在描述新生儿反应的这些方面，以确定反应的哪个组成部分受到来自过敏和非过敏以及rsv免疫和非免疫母亲的母体免疫的影响。2-阐明母体免疫影响新生儿对呼吸道合胞病毒感染反应的潜在机制。研究将确定如何介导母体免疫的影响，以及它如何有助于形成新生儿对呼吸道合胞病毒感染的反应。3-确定母体免疫是否影响新生儿感染呼吸道合胞病毒后对过敏原暴露的反应。RSV感染增强过敏原介导的气道功能障碍。研究将确定母体免疫是否以及如何通过影响新生儿对呼吸道合胞病毒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RSV毛细支气管炎发病风险及后代相关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进哮喘和过敏性气道疾病的发病机制是开发有效治疗方法以预防或治愈疾病的先决条件。