Pathogenesis of M.pneumoniae Reactive Airway Disease

肺炎支原体反应性气道疾病的发病机制

• 批准号: 6846095
• 负责人: ROBERT DOUG HARDY
• 金额: $ 11.88万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6846095
• 关键词: Mycoplasma pneumoniae; asthma; bacteria infection mechanism; cellular immunity; cytokine; disease /disorder model; enzyme linked immunosorbent assay; flow cytometry; gene targeting; genetically modified animals; immunocytochemistry; in situ hybridization; inflammation; interferon gamma; interleukin 12; laboratory mouse; pathologic process; plethysmography; polymerase chain reaction; respiratory airflow disorder; respiratory infections

DESCRIPTION (provided by applicant): The incidence and prevalence of asthma has dramatically increased in the last decades. The CDC estimated that in 1998 asthma affected approximately 17 million people in the United States or 6.4% of the population. Mycoplasma pneumoniae is recognized as a common etiologic agent of acute lower respiratory infection in children and adults. More recently M. pneumoniae has been associated with reactive airway disease and asthma. To study the pathogenesis of M. pneumoniae infection in the respiratory tract and its potential role in asthma, we have established a murine model of acute and chronic M. pneumoniae respiratory infection that manifests airway obstruction, airway hyperreactivity, and pulmonary inflammation. Results from our initial studies, as well as from other investigators, indicate that the production of TH1 and TH2 cytokines in the lower respiratory tract may play an important role in both the acute manifestations and chronic sequelae of M. pneumoniae infection. The central hypothesis of this proposal is that M. pneumoniae lower respiratory tract infection leads to alterations in the pulmonary expression of TH1 and TH2 cytokines and that these cytokines are involved in the development of airway obstruction, increased airway hyperreactivity, and histologic inflammation. We believe that this research may ultimately result in new immunomodulatory strategies to treat children and adults with infection-associated reactive airway disease and asthma. The immediate career goal of the candidate is to procure further training in basic science investigation that will enhance his research skills and allow him to become an independent investigator. As a career focus, the candidate intends to concentrate on the immunopathogenesis of the host microbial pathogen relationship. To achieve this goal, the research proposal calls for the attainment of new scientific technical and intellectual skills while concurrently investigating a timely research topic. The University of Texas Southwestern Medical Center provides a fertile environment both in terms of laboratory assets and experienced, committed faculty necessary for this research and the candidate's career development. This award will facilitate and ensure the eventual transition of the candidate into an independent, academic physician-scientist.

描述（由申请人提供）：过去几十年来，哮喘的发病率和患病率急剧增加。疾病预防控制中心估计，1998 年美国大约有 1700 万人受到哮喘影响，占总人口的 6.4%。肺炎支原体被认为是儿童和成人急性下呼吸道感染的常见病原体。最近，肺炎支原体与反应性气道疾病和哮喘有关。为了研究呼吸道肺炎支原体感染的发病机制及其在哮喘中的潜在作用，我们建立了急性和慢性肺炎支原体呼吸道感染的小鼠模型，该模型表现为气道阻塞、气道高反应性和肺部炎症。我们的初步研究结果以及其他研究人员的结果表明，下呼吸道中 TH1 和 TH2 细胞因子的产生可能在肺炎支原体感染的急性表现和慢性后遗症中发挥重要作用。该提议的中心假设是肺炎支原体下呼吸道感染导致 TH1 和 TH2 细胞因子肺部表达的改变，并且这些细胞因子参与气道阻塞、气道高反应性增加和组织学炎症的发生。我们相信这项研究最终可能会产生新的免疫调节策略来治疗患有感染相关反应性气道疾病和哮喘的儿童和成人。 候选人的近期职业目标是获得基础科学研究方面的进一步培训，这将提高他的研究技能，并使他成为一名独立调查员。作为职业重点，候选人打算专注于宿主微生物病原体关系的免疫发病机制。为了实现这一目标，研究提案要求获得新的科学技术和智力技能，同时研究及时的研究课题。德克萨斯大学西南医学中心为这项研究和候选人的职业发展提供了一个肥沃的环境，无论是实验室资产还是经验丰富、忠诚的教师队伍。该奖项将促进并确保候选人最终转变为独立的学术医师科学家。