Role of Surfactant in Mycoplasma Pulmonary Infection and Exacerbation

描述(由申请人提供)：假设：本建议中要检验的总体假设是，SP-A通过调节从先天免疫到获得性免疫的转变，在肺宿主对肺炎支原体(MP)感染的防御和呼吸道反应性方面发挥重要的保护作用。具体目的：(1)研究SP-A在调节DC成熟和细胞因子调节中的作用，以应对体外的肺炎支原体感染；(2)确定SP-A是否作为调理素并帮助未成熟的DC和肺泡巨噬细胞摄取肺炎支原体，从而在减少上皮结合的同时增加对宿主的清除；(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高反应性的影响，以更好地了解SP-A在实验性哮喘发病中的作用。研究设计：通过对野生型和SP-A缺失型小鼠骨髓来源的树突状细胞的培养，首先研究SP-A在调节MP诱导的DC成熟和细胞因子调节中的作用。然后将使用感染肺炎支原体的SP-A缺陷小鼠来评估这些参数。我将进行更全面的实验，检测MP的清除、摄取和上皮损伤，并确定SP-A是否介导这些活动。使用SP-A基因缺失的实验性过敏性哮喘小鼠的实验将被用来研究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往疾病的恶化到疾病的发展和持续。先天免疫系统和获得性免疫系统之间的相互作用可能在最终决定哮喘的表型表现方面起关键作用。表面活性蛋白在哮喘中的作用尚未得到广泛研究，但已知其在宿主防御和调节炎症中发挥重要作用，这可能有助于哮喘的发展和持续。该项目中提出的研究将有助于阐明表面活性蛋白-A在肺炎支原体肺部感染中的作用，这些感染与哮喘相关的症状特别相关。

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.