Chlamydia pneumoniae is an etiology of acute respiratory diseases in humans. In addition, C.pneumoniae has been associated with chronic respiratory diseases and some diseases of immunopathology. The mechanisms by which C.pneumoniae infections trigger these immunopathologic diseases are largely unknown. The clinical spectrum of C.pneumoniae infection has been extended to atherosclerosis and related clinical manifestations such as coronary heart disease, the number one killer in the U.S. By multiple methods, evidence of the organism has been found in atheromas throughout the arterial tree. If the organism is shown to play a role in atherogenesis, there will be an urgent need to identify vaccine candidates and to develop rapid diagnostic methods. These measures should be aided by elucidation of those factors contributing to C.pneumoniae pathogenesis. There is a paucity of information available on virulence factors of C.pneumoniae and potential targets for prevention of infection. The proposal will seek through molecular, functional, and antigenic analyses to determine the role of following putative virulence factors by: 1) identifying and characterizing the antigens recognized by the C.pneumoniae specific monoclonal antibody because this antibody recognizes surface antigens, has infectivity neutralizing activity, and reacts specifically with C.pneumoniae; 2) identifying the C.pneumoniae antigen which elicits C.pneumoniae specific neutralizing antibodies: a 98-kDa and 42-kDa antigens containing C.pneumoniae specific reactivities recognized during human infection which are also found in circulating immune complexes in persons with coronary artery disease; 3) characterizing a novel genus chlamydial 70-kDa albumin like protein that contains neutralizing epitopes. The hypothesis of antigen mimicry will be addressed by screening sera collected from past studies on immunopathologic diseases associated with chlamydial infection. The ultimate goals of these studies are to elucidating C.pneumoniae antigens contributing to pathogenesis and immunonopathologies that will direct future studies of developing measures for prevention, intervention, and diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043060-03
Application #
6170907
Study Section
Special Emphasis Panel (ZRG5-TMP (02))
Program Officer
Taylor, Christopher E,
Project Start
1998-04-01
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$249,184
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Public Health
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Campbell, Lee Ann; Rosenfeld, Michael E (2015) Infection and Atherosclerosis Development. Arch Med Res 46:339-50
Cabbage, Sarah; Ieronimakis, Nicholas; Preusch, Michael et al. (2014) Chlamydia pneumoniae infection of lungs and macrophages indirectly stimulates the phenotypic conversion of smooth muscle cells and mesenchymal stem cells: potential roles in vascular calcification and fibrosis. Pathog Dis 72:61-9
Campbell, Lee A; Lee, Amy W; Rosenfeld, Michael E et al. (2013) Chlamydia pneumoniae induces expression of pro-atherogenic factors through activation of the lectin-like oxidized LDL receptor-1. Pathog Dis 69:1-6
Campbell, Lee Ann; Puolakkainen, Mirja; Lee, Amy et al. (2012) Chlamydia pneumoniae binds to the lectin-like oxidized LDL receptor for infection of endothelial cells. Microbes Infect 14:43-9
Jiang, Shinn-Jong; Kuo, Cho-Chou; Berry, Mark W et al. (2008) Identification and characterization of Chlamydia pneumoniae-specific proteins that activate tumor necrosis factor alpha production in RAW 264.7 murine macrophages. Infect Immun 76:1558-64
Takaoka, Naohisa; Campbell, Lee Ann; Lee, Amy et al. (2008) Chlamydia pneumoniae infection increases adherence of mouse macrophages to mouse endothelial cells in vitro and to aortas ex vivo. Infect Immun 76:510-4
Puolakkainen, Mirja; Lee, Amy; Nosaka, Tadayoshi et al. (2008) Retinoic acid inhibits the infectivity and growth of Chlamydia pneumoniae in epithelial and endothelial cells through different receptors. Microb Pathog 44:410-6
Kuo, Cho-Chou; Lee, Amy; Jiang, Shinn-Jong et al. (2007) Inoculation of Chlamydia pneumoniae or Chlamydia trachomatis with ligands that inhibit attachment to host cells reduces infectivity in the mouse model of lung infection: implication for anti-adhesive therapy. Microbes Infect 9:1139-41
Campbell, Lee Ann; Lee, Amy; Kuo, Cho-chou (2006) Cleavage of the N-linked oligosaccharide from the surfaces of Chlamydia species affects infectivity in the mouse model of lung infection. Infect Immun 74:3027-9
Puolakkainen, Mirja; Kuo, Cho-Chou; Campbell, Lee Ann (2005) Chlamydia pneumoniae uses the mannose 6-phosphate/insulin-like growth factor 2 receptor for infection of endothelial cells. Infect Immun 73:4620-5

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