Chlamydia trachomatis is responsible for a significant proportion of pelvic inflammatory disease (PID) in women. Often chlamydial PID goes unrecognized, yet infection leads to significant sequelae, including adverse pregnancy outcome and obstructive infertility. Chlamydia have been difficult to culture from women with upper genital tract disease, especially after the disease process has become chronic, but evidence is accumulating to indicate that chlamydial genomes continue to be present in diseased upper genital tract tissue of the endometrium and fallopian tubes. We propose that C. trachomatis is present in a culture negative state during these disease processes and can persist within host cells of the genital tract in an atypical form, for prolonged periods of time. We further propose that the particular characteristics of these atypical, persistent chlamydia actually contribute to the disease process by eliciting inflammation and/or delayed type hypersensitivity responses. Our hypothesis is that inflammatory and/or immune-regulated cytokines alter chlamydial host cells in a way that causes persistent chlamydia to develop and that understanding the biochemical attributes of persistent chlamydia will help to better understand the complicated pathogenesis of chronic upper genital tract disease in women. It is not clear if chlamydia can maintain a presence in cells other than the genital epithelium, but as a starting point we propose to study cytokine-mediated changes in polarized human endometrial epithelial cells that may lead to chlamydial persistence, characterize persistent chlamydia at the structural and biochemical level and determine how these atypical organisms may contribute to the disease process and cause upper genital tract infections to be difficult to recognize and manage appropriately.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Kalayoglu, Murat V; Libby, Peter; Byrne, Gerald I (2002) Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. JAMA 288:2724-31
Kalayoglu, M V; Perkins, B N; Byrne, G I (2001) Chlamydia pneumoniae-infected monocytes exhibit increased adherence to human aortic endothelial cells. Microbes Infect 3:963-9
Kim, S K; DeMars, R (2001) Epitope clusters in the major outer membrane protein of Chlamydia trachomatis. Curr Opin Immunol 13:429-36
Kim, S K; Devine, L; Angevine, M et al. (2000) Direct detection and magnetic isolation of Chlamydia trachomatis major outer membrane protein-specific CD8+ CTLs with HLA class I tetramers. J Immunol 165:7285-92
Ortiz, L; Angevine, M; Kim, S K et al. (2000) T-cell epitopes in variable segments of Chlamydia trachomatis major outer membrane protein elicit serovar-specific immune responses in infected humans. Infect Immun 68:1719-23
LaVerda, D; Kalayoglu, M V; Byrne, G I (1999) Chlamydial heat shock proteins and disease pathology: new paradigms for old problems? Infect Dis Obstet Gynecol 7:64-71
Kim, S K; Angevine, M; Demick, K et al. (1999) Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections. J Immunol 162:6855-66
Kane, C D; Vena, R M; Ouellette, S P et al. (1999) Intracellular tryptophan pool sizes may account for differences in gamma interferon-mediated inhibition and persistence of chlamydial growth in polarized and nonpolarized cells. Infect Immun 67:1666-71
Kalayoglu, M V; Byrne, G I (1998) A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun 66:5067-72
Kalayoglu, M V; Byrne, G I (1998) Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis 177:725-9

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