This application proposes to study Chlamydia trachomatis infection in a new experimental monkey model (subcutaneous model) in which monkeys are inoculated with the organisms into subcutaneous homografts of oviductal tissues. The objectives are to elucidate the immunopathology of C. trachomatis salpingitis and the pathogenesis of its sequela, tubal infertility, and to evaluate the immunity against infection and the prevention of infection by immunization.
The specific aims are 1) to define the clinical course of infection by cell culture isolation of the organisms, detection of chlamydial antigens in tissue by immunofluorescence and immunoperoxidase stains, measurement of serum antibody response by the indirect immunofluorescent antibody test, and histopathological electron microscopic study of tissue biopsy, 2) to observe the effect of female sex hormones on the susceptibility of the fallopian tissue to infection and the course of infection by timing the inoculation to the estrogen or progesterone phase in the animals artificially cycled with hormone implant after oophorectomy, 3) to determine whether monkeys recovered from the primary infection will develop resistance against rechallenge inoculation, 4) to study the pathogenesis of tubal infertility by analyzing the histopathological changes of inflammatory response with the tissue sections stained with Hematoxylin & Eosin stain for routine histology and with immunofluorescence and immunoperoxidase stains for detection of chlamydial antigens and identification of infiltrating lymphocyte subclasses, 5) to assess the immunity, both acquired after infection and induced by immunization, and its specificity by homologous and heterologous rechallenge inoculation, and 6) to evaluate the effectiveness and deleterious effect of vaccine by immunization with purified formalin inactivated whole organism vaccine or fractionated antigen vaccine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI022082-01
Application #
3132758
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
1
Fiscal Year
1985
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