Project 2: Environmental Determinants of Early Host Response to RSV

众所周知，臭氧等吸入空气污染物会加剧哮喘，并可能在 早期出现反应性AIN/VAY病。虽然臭氧会导致严重的呼吸道健康 问题在大多数接触过的人中，幼儿尤其有更大的风险发展 臭氧暴露对健康造成的严重不良影响。这是因为他们的肺还在快速发育， 而在这一关键的易感窗口期间暴露可能会改变肺部发育，导致 永久性的呼吸道健康问题。空气污染物也可能影响人体发育中的免疫系统 幼儿，增加对感染的敏感性，并促进对常见空气过敏原的主要致敏作用。 这个项目的总体目标是定义臭氧如何影响肺部发育和宿主。 出生后早期的免疫反应。我们的一般假设是，早期的臭氧暴露 出生后阶段改变肺发育并改变宿主对早期生命病毒的免疫反应 感染和过敏原暴露，从而促进反应性呼吸道疾病的发展。 为了验证这一假设，我们将追求以下目标： 1.明确臭氧对机体天然免疫应答、AIN/VAY结构和功能的影响。研究是 旨在识别哪些Toll样受体(TLRs)在出生后暴露于臭氧后被修饰，以 明确Away结构和功能的变化，并确定TLR-4在这些反应中的作用。 2.明确臭氧对呼吸道合胞病毒(RSV)感染早期宿主反应的影响 和屋尘螨(HDM)过敏原暴露。拟议中的研究将确定臭氧如何改变 宿主在出生后阶段对RSV和HDM的反应，并将定义相关的呼吸道变化 TLR-4的结构和功能以及在这些反应中的作用。 3.为了确定与TLR-4相互作用的空气污染物--脂多糖(LPS)如何改变 出生后臭氧暴露后宿主对RSV和HDM的反应。我们将确定内毒素如何修改 早期宿主对RSV和HDM的反应，以及与之相关的呼吸道结构和功能的变化， 在出生后接触臭氧之后。

Inhaled air pollutants such as ozone are known to exacerbate asthma and may play a potential role in the inception of reactive ain/vay disease in early life. While ozone can cause significant respiratory health problems in the majority of exposed individuals, young children are particularly at greater risk for developing serious adverse health effects from ozone exposure. This is because their lungs are still developing rapidly, and exposures during this critical window of susceptibility may alter lung development, resulting in permanent respiratory health problems. Air pollutants may also influence the developing immune system in young children, increasing susceptibility to infection and promoting ainway sensitization to common aeroallergens. The overall objective of this project is to define how ozone influences lung development and host immune response in early postnatal life. Our general hypothesis is that ozone exposure in the early postnatal phase alters lung development and modifies the host immune response to early life viral infection and allergen exposure, thereby contributing to the development of reactive airway disease. To test this hypothesis, we will pursue the following aims: 1. To define the influence of ozone on innate immune response, ain/vay structure and function. Studies are designed to identify which toll-like receptors (TLRs) are modified following postnatal ozone exposure, to define the changes in ainway structure and function, and to determine the role of TLR-4 in these responses. 2. To define the influence of ozone on the early host response to respiratory syncytial virus (RSV) infection and house dust mite (HDM) allergen exposure. The proposed studies will determine how ozone modifies the host response to RSV and HDM during the postnatal phase and will define the associated changes in airway structure and function and the role of TLR-4 in these responses. 3. To determine how lipopolysaccharide (LPS), an air contaminant that interacts with TLR-4, modifies the host response to RSV and HDM following postnatal ozone exposure. We will determine how LPS modifies the early host response to RSV and HDM, and associated changes in ainway structure and function, following postnatal ozone exposure.