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.
