Chlamydia trachomatis is at present one of the most common sexually transmitted pathogens and has been established as an important cause of salpingitis. Salpingitis is one of the most severe forms of chlamydial infection in women often resulting in tubal scarring, a leading cause of preventable infertility. Little is known about the pathogenesis of chlamydial salpingitis in the human. To study chlamydial salpingitis, we have established a new animal model: the subcutaneous pocket model of oviductal tissue autografts in monkeys. The objectives of the proposed study are to elucidate the immunopathology of C. trachomatis salpingitis, and to evaluate immunity against infection and prevention of infection by immunization.
The specific aims are to: 1) define the ultrastructure of attachment, entry, and development of C. trachomatis in vivo by transmission electron microscopy; 2) assess persistent infection and correlate inflammatory reactions and tissue damage with infection by culture, detection of chlamydial antigens and DNA, and reactivation; 3) identify and quantitate components of the cell mediated immune response by immunocytology and flow cytometry and by administration of cytokines; 4) evaluate the role of hypersensitivity reactions and analyze the antigens that cause hypersensitivity by injecting different antigens into sensitized pockets; 5) evaluate the effects of oral contraceptives on susceptibility of the female reproductive tract to infection with C. trachomatis and on inflammatory reactions; and 6) study the immunity and prevention of infection by vaccine of chlamydial salpingitis by immunization with inactivated whole organisms or fractionated antigens followed by inoculation with live organisms in the pockets to determine the specificity and duration of immunity, and to develop effective methods of immunization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI022082-04A3
Application #
3132762
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1985-09-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Public Health
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Lichtenwalner, Anne B; Patton, Dorothy L; Van Voorhis, Wesley C et al. (2004) Heat shock protein 60 is the major antigen which stimulates delayed-type hypersensitivity reaction in the macaque model of Chlamydia trachomatis salpingitis. Infect Immun 72:1159-61
Van Voorhis, W C; Barrett, L K; Sweeney, Y T et al. (1997) Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes produces a Th1-like cytokine response associated with fibrosis and scarring. Infect Immun 65:2175-82
Van Voorhis, W C; Barrett, L K; Sweeney, Y T et al. (1996) Analysis of lymphocyte phenotype and cytokine activity in the inflammatory infiltrates of the upper genital tract of female macaques infected with Chlamydia trachomatis. J Infect Dis 174:647-50
Cappuccio, A L; Patton, D L; Kuo, C C et al. (1994) Detection of Chlamydia trachomatis deoxyribonucleic acid in monkey models (Macaca nemestrina) of salpingitis by in situ hybridization: implications for pathogenesis. Am J Obstet Gynecol 171:102-10
Patton, D L; Sweeney, Y T; Kuo, C C (1994) Oral contraceptives do not alter the course of experimentally induced chlamydial salpingitis in monkeys. Sex Transm Dis 21:89-92
Patton, D L; Sweeney, Y T; Kuo, C C (1994) Demonstration of delayed hypersensitivity in Chlamydia trachomatis salpingitis in monkeys: a pathogenic mechanism of tubal damage. J Infect Dis 169:680-3
Patton, D L; Cosgrove, Y T; Kuo, C C et al. (1993) Effects of quinolone analog CI-960 in a monkey model of Chlamydia trachomatis salpingitis. Antimicrob Agents Chemother 37:8-13
Patton, D L; Kuo, C C; Brenner, R M (1989) Chlamydia trachomatis oculogenital infection in the subcutaneous autotransplant model of conjunctiva, salpinx and endometrium. Br J Exp Pathol 70:357-67
Patton, D L; Kuo, C C (1989) Histopathology of Chlamydia trachomatis salpingitis after primary and repeated reinfections in the monkey subcutaneous pocket model. J Reprod Fertil 85:647-56
Patton, D L; Kuo, C C; Wang, S P et al. (1987) Chlamydial infection of subcutaneous fimbrial transplants in cynomolgus and rhesus monkeys. J Infect Dis 155:229-35