The theme of this program project is the examination of mechanisms and consequences of the phlogistic or inflammatory effects of infecting bacteria, notably C. trachomatis and N. gonorrhoeae, in the evolution of pelvic inflammatory disease (PID). The project is subdivided into a core and 5 separate research proposals. These projects will: (1) determine the risk of transmission of C. trachomatis and N. gonorrhoeae from men to women; (2) determine the risk of acquiring PID after infection with one of these agents (Project 1); and (3) determine the course of treated PID when alternative therapeutic regimens are used (Project 2). In Project 3, the immune interactions of N. gonorrhoeae with human hosts will be studied. This study is designed principally to identify immunologic factors in secretions and serum that contribute to the gonococcus' ability to incite inflammatory mechanisms. The epidemiologic design of this study is derived from Project 1. In addition, Project 1 will also serve as a source of patients and controls for studies that parallel those in gonorrhea patients (Project 3) that will be performed in patients infected or exposed to C. trachomatis. These investigations will be conducted as part of Project 4. Human secretions will be examined for the presence of chlamydial immune complexes in addition to antibodies directed against genus and type specific antigens. The genus specific glycolipid antigen of C. trachomatis may play a phlogistic role in PID similar to more established evidence that implicates lipooligosacharides (LOSs) of N. gonorrhoeae as an inciting antigen. These antigens will be isolated, characterized and also examined for their role in mechanisms of infection using in vitro models of epithelial invasion. In Project 5, a combined biochemical and immunologic tactic will be taken to examine ability of C. trachomatis to stimulate biochemical events in another eucaryotic cell, the human neutrophil. Antibody directed against Chlamydia antigens, and perhaps complement (C), influence these events. These opsonins may promote ingestion of elementary bodies by the neutrophil and then stimulate the respiratory burst, which may be accompanied by degranulation and release of intracellular enzymes. These mechanisms will be elucidated.
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