: Chlamydia pneumoniae is a human respiratory pathogen that causes 5 percent to 10 percent of pneumonia, bronchitis, and sinusitis. Virtually everyone is infected in his or her lifetime and reinfection is common. Infection is difficult to treat even with sensitive antibiotics. Chronic infection is common and has been associated with asthma, reactive airway disease, Reiter's syndrome, erythema nodosum, and sarcoidosis. The potential public health impact of infection with this pathogen is underscored by the association of C. pneumoniae with atherosclerosis and related clinical manifestations such as coronary heart disease, carotid artery stenosis, aortic aneurysm, claudication, and stroke. If C. pneumoniae infection plays a role in atherogenesis, there will be an urgent need to facilitate diagnosis and develop strategies for intervention and prevention. The overall goal of this proposal is two fold. First, C. pneumoniae specific antigens that are recognized during human infection will be exploited to facilitate serodiagnosis and identify putative vaccine candidates. The second goal is to define chlamydial/host cell interactions that lead to entry and survival of C. pneumoniae in host cells relevant to atherosclerosis. The specific focus will be on the interaction of the chlamydial glycan moiety with carbohydrate binding receptors on the host cell. Importantly, infection of epithelial cells can be inhibited with N-linked high mannose type oligosaccharide, the major component of the glycan. The novel hypothesis to be tested is that C. pneumoniae enters through the mannose-6 phosphate receptor by binding to the site involved in transport of phosphomannosylated residues to the lysosome and this differs from C. trachomatis, which utilizes the mannose receptor. The ultimate goals of these studies are to identify C. pneumoniae specific antigens to facilitate laboratory diagnosis and virulence factors playing a role in pathogenesis to guide vaccine development or develop anti-adhesive strategies for prevention of infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI043060-05
Application #
6472104
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Taylor, Christopher E,
Project Start
1998-04-01
Project End
2007-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
5
Fiscal Year
2002
Total Cost
$341,325
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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