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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08AI052262-01A1
Application #
6612598
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Taylor, Christopher E,
Project Start
2003-05-01
Project End
2008-01-31
Budget Start
2003-05-01
Budget End
2004-01-31
Support Year
1
Fiscal Year
2003
Total Cost
$108,000
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Salvatore, C M; Fonseca-Aten, M; Katz-Gaynor, K et al. (2008) Intranasal interleukin-12 therapy inhibits Mycoplasma pneumoniae clearance and sustains airway obstruction in murine pneumonia. Infect Immun 76:732-8
Salvatore, C M; Fonseca-Aten, M; Katz-Gaynor, K et al. (2007) Respiratory tract infection with Mycoplasma pneumoniae in interleukin-12 knockout mice results in improved bacterial clearance and reduced pulmonary inflammation. Infect Immun 75:236-42
Michelow, Ian C; Katz, Kathy; McCracken, George H et al. (2007) Systemic cytokine profile in children with community-acquired pneumonia. Pediatr Pulmonol 42:640-5
Woolard, Matthew D; Hardy, R Doug; Simecka, Jerry W (2004) IL-4-independent pathways exacerbate methacholine-induced airway hyperreactivity during mycoplasma respiratory disease. J Allergy Clin Immunol 114:645-9