Disease Outcome Subsequent to Primary and Secondary Urogenital Infection with Murine or Human Biovars of<i>Chlamydia trachomatis</i>

Ramsey, Kyle H.; DeWolfe, Jennifer; Salyer, Rena D.

doi:10.1128/iai.68.12.7186-7189.2000

Cited by 23 publications

(20 citation statements)

References 14 publications

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“…Uterine edema and cell vacuolization as well as oviduct cell vacuolization and hyperplasia were observed. Lesions were similar to those observed by Ramsey et al (2000) (18) following a primary murine intravaginal infection with a C. trachomatis serovar E strain.…”

Section: Vol 73 2005 Chlamydia Trachomatis Infection Model 8319supporting

confidence: 73%

Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection

et al. 2005

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The purpose of the present study was to evaluate pigs as a large-animal model for female genital infection with two Chlamydia trachomatis human serovar E strains. Sixteen-week-old specific-pathogen-free female pigs (gilts) were intravaginally infected with the trachoma type E reference strain Bour or the urogenital serovar E strain 468. Several conclusions can be drawn from our findings on the pathogenicity of a primary C. trachomatis genital infection in gilts. First of all, we demonstrated that the serovar E strains Bour and 468 could ascend in the genital tract of gilts. The serovar E strains could replicate in the superficial columnar cervical epithelium and in the superficial epithelial layer of the uterus, which are known to be the specific target sites for a C. trachomatis genital infection in women. Second, inflammation and pathology occurred at the replication sites. Third, the organisms could trigger a humoral immune response, as demonstrated by the presence of immunoglobulin M (IgM), IgG, and IgA in both serum and genital secretion samples. Our findings imply that the pig model might be useful for studying the pathology, pathogenesis, and immune response to a C. trachomatis infection of the genital system.Chlamydia trachomatis continues to be the most common cause of sexually transmitted disease in developed countries. World Health Organization figures estimated that over 90 million new cases of C. trachomatis infection occur worldwide each year. C. trachomatis infection of the genital tract often results in pelvic inflammatory disease, ectopic pregnancy, chronic pelvic pain, epididymitis, and infant pneumonia (20). C. trachomatis genital tract infections may also increase the risk for human immunodeficiency virus infection (9). Differences in clinical courses of infection, resulting in either symptomatic or asymptomatic infections, are observed. Bacterial and host factors are believed to contribute to these differences in clinical courses, although further research is needed (11).So far, no vaccine has been available, but studies that may lead to the development of a highly warranted vaccine have been performed. The first attempt to vaccinate children with a whole-cell vaccine initially resulted in protection, but the protection was short-lived. In animal models, whole-cell vaccination resulted in hypersensitivity reactions, so new strategies were devised. The first immunogenic molecule described was the major outer membrane protein, and this molecule has therefore been studied in great detail as a candidate vaccine. Even though complete protection was not obtained, reduced shedding was observed, and vaccine trials in animal models using naked DNA as a vaccine resulted in stimulation of both the humoral and the cellular immune responses, indicating progress in vaccine development (3).A pig model of infection would be helpful both for vaccine studies and for studies on major determinants of C. trachomatismediated pathogenesis. Pigs are physiologically and genetically closely related to humans (1, 21),...

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Section: Vol 73 2005 Chlamydia Trachomatis Infection Model 8319supporting

confidence: 73%

Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection

et al. 2005

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“…The development of infertility subsequent to MoPn infection has been used to delineate susceptible and resistant strains of mice and as a further measure of pathological outcome that may be related to hydrosalpinx formation (14,26). Fifty-six days subsequent to infection, all mice were assessed for fertility with an adaptation of the method of De La Maza et al (14).…”

Section: Methodsmentioning

confidence: 99%

Chlamydia trachomatisPersistence in the Female Mouse Genital Tract: Inducible Nitric Oxide Synthase and Infection Outcome

et al. 2001

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It was previously reported that female mice resolve a primary Chlamydia trachomatis urogenital infection independent of inducible nitric oxide synthase (iNOS). We now report that although iNOS-deficient (NOS2 ؊/؊ ) mice resolve culture-apparent infection in a fashion similar to that of normal control (NOS2 ؉/؉ ) mice, they sustain significantly increased rates of disease, as assessed by hydrosalpinx formation. PCR amplification of ompA followed by Southern blot detection of amplicands revealed the presence of chlamydial DNA in the lower genital tracts of both NOS2؊/؊ and NOS2 ؉/؉ mice at >120 days postinfection and in upper genital tract tissues at >120 days postinfection. However, only NOS2 ؊/؊ mice shed low numbers of viable chlamydiae from the lower genital tract after immunosuppressive treatment at 120 days postinfection. When cultured primary murine lung fibroblasts were activated in the presence of gamma interferon (IFN-␥), inhibition of chlamydial growth occurred in both NOS2؉/؉ and NOS2 ؊/؊ cells, but the inhibition was reversible after removal of the cytokine in the NOS2 ؊/؊ primary cell culture only. The iNOS-independent inhibition was microbistatic but was independent of 2,3-indoleamine dioxygenase activity. We conclude that chlamydial DNA and antigens persist in mice subsequent to culture-apparent resolution. In addition, IFN-␥ induces in vivo inhibition of chlamydial growth through microbistatic mechanisms in the absence of iNOS activity, but in the presence of iNOS activity, IFN-␥ is microbicidal and effects eradication.

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“…muridarum infects various strains of mice nearly equally (23,56,89). Some strains have a higher propensity for the development of hydrosalpinx and shed somewhat greater numbers of bacteria, but overall rates of infection are more or less equivalent.…”

Section: Historical Vaccine Studiesmentioning

confidence: 99%

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

2011

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2Chlamydia trachomatis genital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model of C. muridarum genital infection has been extremely useful for identification of protective immune responses and in vaccine development. Although a number of immunogenic antigens have been assessed for their ability to induce protection, the majority of studies have utilized the whole organism, the major outer membrane protein (MOMP), or the chlamydial protease-like activity factor (CPAF). These antigens, alone and in combination with a variety of immunostimulatory adjuvants, have induced various levels of protection against infectious challenge, ranging from minimal to nearly sterilizing immunity. Understanding of the mechanisms of natural infection-based immunity and advances in adjuvant biology have resulted in studies that are increasingly successful, but a vaccine licensed for use in humans has not yet been brought to fruition. Here we review immunity to chlamydial genital infection and vaccine development using the C. muridarum model.Chlamydia trachomatis, a Gram-negative obligate intracellular bacterium with a tropism for mucosal epithelial cells, is the most common cause of bacterial sexually transmitted disease in both developed and developing countries, with more than 90 million new cases occurring each year (113-115). More than 4 million new cases of C. trachomatis infection occur each year in the United States, where costs associated with treating those infections and associated complications are in excess of $2 billion annually (107). In the genital tract, infection with C. trachomatis is propagated within the single-cell columnar layer of the epithelium in the urethra of men and the endocervix of women. Within the epithelial cells, C. trachomatis undergoes a unique biphasic developmental cycle consisting of an infectious, but metabolically inert elementary body (EB) and a noninfectious, but metabolically active reticulate body (RB). After completion of the developmental cycle, the EBs are released and infect neighboring epithelial cells, thereby spreading the infection.Infection can result in acute inflammation characterized by redness, edema, and mucosal discharge and is diagnosed clinically as mucopurulent cervicitis in women and nongonococcal urethritis in men (10, 85). In women, infection can manifest as abnormal vaginal discharge and/or postcoital bleeding, while the infection is limited to the lower genital tract, and irregular uterine bleeding and/or pelvic discomfort once the infection ascends to the upper genital tract (85). Symptoms in males are generally limited to dysuria and moderate clear-to-whitish discharge (85). While these symptoms signify an infection, the absence of such symptoms does not necessarily indicate the absence of infection. It is estimated that Ͼ70% of women and 50% of men experience asymptomatic infections (15,113). Without symptoms providing the impetus, asymptomatic individuals may not seek ...

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Disease Outcome Subsequent to Primary and Secondary Urogenital Infection with Murine or Human Biovars ofChlamydia trachomatis

Cited by 23 publications

References 14 publications

Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection

Specific-Pathogen-Free Pigs as an Animal Model for Studying Chlamydia trachomatis Genital Infection

Chlamydia trachomatisPersistence in the Female Mouse Genital Tract: Inducible Nitric Oxide Synthase and Infection Outcome

Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel

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