Role of Surfactant in Mycoplasma Pulmonary Infection and Exacerbation

描述（由申请人提供）：假设：本提案要验证的总体假设是SP-A通过调节从先天免疫到适应性免疫的转变，在肺宿主防御肺炎支原体（MP）感染和气道反应性中起重要的保护作用。具体目的：(1)研究SP-A在体外肺炎支原体感染中调控DC成熟和细胞因子调节的作用；(2)确定SP-A是否作为一种调理素，帮助未成熟dc和肺泡巨噬细胞摄取肺炎支原体，从而增加清除率，同时减少上皮结合和对宿主的伤害；(3)利用SP-A缺乏的小鼠研究SP-A对肺炎支原体诱导的气道多动的影响，以更好地了解SP-A在实验性哮喘中的作用。研究设计：SP-A在调节mp诱导的DC成熟和细胞因子调节中的作用将首先通过研究野生型和SP-A缺失小鼠培养的骨髓来源树突状细胞来研究。然后用感染肺炎支原体缺乏SP-A的小鼠来评估这些参数。我将进行更全面的实验，检查MP清除、摄取和上皮损伤，并确定SP-A是否介导这些活动。实验将采用SP-A缺失的实验性过敏性哮喘小鼠，研究SP-A在MP诱导的哮喘加重中的作用。相关性：过敏原、感染和哮喘之间的关系包括从既定疾病的恶化到疾病的发展和持续存在的一系列关系。先天免疫系统和适应性免疫系统之间的相互作用可能是最终决定哮喘表型表现的关键。表面活性剂蛋白在哮喘中的研究还不广泛，但已知在宿主防御和炎症调节中发挥重要作用，这可能有助于哮喘的发展和持续。本项目的研究将有助于阐明表面活性剂蛋白a在肺炎支原体肺部感染中与哮喘相关症状特异性相关的作用。

DESCRIPTION (provided by applicant): Hypothesis: The overall hypothesis to be tested in this proposal is that SP-A plays an important protective role in pulmonary host defense against M. pneumoniae (MP) infections and airway reactivity by modulating the transition from innate to adaptive immunity. Specific Aims: (1) to investigate the role of SP-A in regulating DC maturation and cytokine modulation in response to M. pneumoniae infection in vitro; (2) to determine if SP-A acts as an opsonin and aids in the uptake of M. pneumoniae by immature DCs and alveolar macrophages, thereby increasing clearance while decreasing epithelial binding and insult to the host; (3) to examine the effects of SP-A on M. pneumoniae induced airway hyperactivity using mice deficient in SP-A to better understand the role of SP-A in an experimental asthma setting. Study Design: The role of SP-A in regulating MP-induced DC maturation and cytokine modulation will first be examined by studying bone marrow derived dendritic cells cultured from wild type and SP-A null mice. These parameters will then be assessed using mice deficient in SP-A infected with M. pneumoniae. I will perform more comprehensive experiments examining MP clearance, uptake and epithelial damage and determine if SP-A mediates these activities. Experiments using SP-A null mice with experimental allergic asthma will be used to study the role of SP-A in MP induced asthma exacerbations. Relevance: The relationship between allergen, infection and asthma comprises a spectrum ranging from exacerbation of established disease to development and persistence of disease. The interactions between the innate and adaptive immune systems may be pivotal in ultimately determining the phenotypic presentation of asthma. Surfactant proteins have not been widely studied in asthma but are known to play important roles in host defense and modulation of inflammation which may contribute to the development and persistence of asthma. The research proposed in this project will aid in elucidating the role of Surfactant Protein-A in M. pneumoniae pulmonary infections specifically associated with asthma related symptoms.