Chlamydia trachomatis remains a significant cause of sexually transmitted disease in the United States and Europe. The major concern with chlamydial genital infections is the development of salpingitis which may result in tubal obstruction and infertility. While the pathogenesis of salpingitis is still not clear, it is basically agreed that the primary site of infection is the endocervix with subsequent canalicular spread to the endometrium and fallopian tubes. Current evidence indicates that ascending infection develops in a significant number of individuals but the reasons why only a certain proportion of women develop clinical salpingitis is not known. Furthermore, the mechanism of salpingitis is undefined, although evidence suggests that multiple occurrences increases the incidence of tubal obstruction. In this study, guinea pigs infected in the genital tract with the chlamydia gent of guinea pig inclusion conjunctivitis (GPIC) will be used as a model system. Intravaginal inoculation of chlaymydiae in the guinea pig results routinely in ascending infection with the development of salpingitis. This phenomenon will be characterized with regard to the dose of GPIC required, the time frame of development of the disease, the cellular makeup of the pathological changes, and the relationship to the stage of the estrous cycle. The effect of multiple infections and the possible immunopathological etiology of salpingitis will be studied. Since prevention of reinfection by immunization with inactivated antigens has not proved wholly successful, the strategy of immunization with the objective of preventing ascending infection and tubal disease will be explored. Guinea pigs will be immunized with inactivated organisms and challenged intravaginally. The effectiveness will be assessed by examination of the fallopian tubes at various times for pathology and chlamydiae. The duration of any protective effect will also be determined. In addition, the possibility of immunopathological sequellae will be evaluated. Finally, specific chlamydial outer membrane components including the major outer membrane component, a 61- kDA protein, and lipopolysaccharide will be isolated and used as immunogens to determine which may possess a protective epitope(s). Further screening studies will be injected into guinea pigs and their protective ability assessed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI023044-04
Application #
3134900
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1986-04-01
Project End
1992-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Mallet, Dann G; Heymer, Kelly-Jean; Rank, Roger G et al. (2009) Chlamydial infection and spatial ascension of the female genital tract: a novel hybrid cellular automata and continuum mathematical model. FEMS Immunol Med Microbiol 57:173-82
Nagarajan, U M; O'Connell, C; Rank, R G (2004) Molecular characterization of guinea - pig (Cavia porcellus) CD8alpha and CD8beta cDNA. Tissue Antigens 63:184-9
Rank, Roger G; Bowlin, Anne K; Reed, Ronald L et al. (2003) Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose. Infect Immun 71:6148-54
Rank, R G; Bowlin, A K; Kelly, K A (2000) Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model. Infect Immun 68:5293-8
Darville, T; Andrews Jr, C W; Rank, R G (2000) Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract infection in mice and guinea pigs? Infect Immun 68:5299-305
Wyrick, P B; Knight, S T; Paul, T R et al. (1999) Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis. J Infect Dis 179:954-66
Patterson, T L; Rank, R G (1996) Immunity to reinfection and immunization of male guinea pigs against urethral infection with the agent of guinea pig inclusion conjunctivitis. Sex Transm Dis 23:145-50
Rank, R G; Dascher, C; Bowlin, A K et al. (1995) Systemic immunization with Hsp60 alters the development of chlamydial ocular disease. Invest Ophthalmol Vis Sci 36:1344-51
Darville, T; Laffoon, K K; Kishen, L R et al. (1995) Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae. Infect Immun 63:4675-81
Rank, R G; Sanders, M M; Patton, D L (1995) Increased incidence of oviduct pathology in the guinea pig after repeat vaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis. Sex Transm Dis 22:48-54

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