Pathogenesis of M.pneumoniae Reactive Airway Disease

描述（由申请人提供）：在过去的几十年里，哮喘的发病率和患病率急剧增加。据美国疾病控制与预防中心估计，1998年美国约有1700万人患有哮喘，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。为了研究肺炎支原体呼吸道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小鼠模型，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者的研究结果表明，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。该建议的中心假设是肺炎支原体下呼吸道感染导致肺中TH1和TH2细胞因子表达的改变，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展。我们相信，这项研究可能最终导致新的免疫调节策略，以治疗儿童和成人感染相关的反应性气道疾病和哮喘。

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.