Sequelae of chlamydial PID include infertility an ectopic pregnancy that occur as a consequence of tubal damage and obstruction. The disease process associated with chlamydial infections is thought to be largely immunologically mediated. A unique persistent form of chlamydiae has been characterized in several cell culture systems and development of persistence has been documented to be driven by immune-regulated cytokines. To effectively study persistence in vivo, an animal model that sufficiently reflects upper genital tract disease is needed. Ideally, this model should exhibit qualities that allow for precise immunologic characterization and be well defined genetically. With these considerations in mind, the murine model for chlamydial PID will be adapted to study the problem of chlamydial persistence. The hypothesis to be tested is that chlamydial persistence is a determining factor in the development of oviduct disease.
The aims of the proposed wok are to adapt and further develop the murine model of PID, to document the presence of persistent chlamydiae in uterine and/or oviduct tissue, to study the effects of immune reactivity on persistence, and to compare mechanisms of persistence induction between human and murine chlamydial host cells in culture. Results of this study will provide information important in understanding the pathogenesis of chlamydial upper genital tract disease, could contribute to improved diagnosis of silent chlamydial PID in women, and may ultimately be useful to rational vaccine development for this important human pathogen.
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