The goal os this program project is to combine appropriate working teams immunologists, molecular geneticists, microbiologists and clinicians to study the molecular immunology of sexually transmitted diseases caused by Chlamydia trachomatis. The decision to work on a single important STD pathogen was deliberate effort to blend talents from a variety of disciplines in such a way to make it possible to comprehensively evaluate the overall immune response to C. trachomatis, especially in the context of progress from uncomplicated lower genital tract infections to sequelae of chronic upper genital tract disease, including involuntary infertility and adverse outcomes of pregnancy in women. Studies are proposed to evaluate, at the molecular level the requirements for processing and presentation of chlamydial antigens, and identification of relevant T cell epitopes (project 1, DeMars) and the nature and function of antigen presenting cells in vivo at the site of upper genital tract disease (project 2, Arno and Bick). Work also is proposed to define the process of chlamydial persistence in human polarized epithelial cells, including primary endometrial cells; how immune reactivity contributes to this process and the molecular characterization of chlamydia as they exist in the persistent state (project 3, Byrne). Finally, work is proposed to determine if protective immunity occurs in individuals who recover from lower genital tract disease; and if so define the requirements based on epitopic specificity of antibody responses that result in protection (project 4, Batteiger). These projects will be served by an administrative core in Madison (Byrne), a clinical core in Indianapolis (Jones) and a peptide synthesis core in Madison (Niece). The overall aim of comprehensively increasing our understanding of immunity to chlamydial genital tract disease will be accomplished by closely networking each of the four research projects with each other, with the core facilities and with collaborators who are directly involved in complementary research programs via STD Center grants. It is anticipated that this focused, comprehensive approach will serve to increase our knowledge in this field in a way that has been difficult because of the lack of coordination of work done in this area. This program project will reduce fragmentation of effort and facilitate a multicenter cooperative effort with clear goals in mind.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI034617-02
Application #
2069775
Study Section
Special Emphasis Panel (SRC (35))
Project Start
1993-09-01
Project End
1998-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
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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