The major objectives of this STD-CRC are directed towards the prevention and control of two major STD pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae in the context of their natural settings-patients infected with these organisms. Five research projects and four service cores (Administrative, Clinical, Laboratory and Statistical) are proposed. In the first project we propose to develop and evaluate an educational intervention to prevent Chlamydia infection among sexually active inner city youths using the populations of two Boston adolescent clinics (Boston Medical Center and Children's Hospital). In the second Project, we propose to use newly developed genetic techniques to identify novel virulence genes and mechanisms focusing particularly on how C. trachomatis regulate their dimorphic life cycle. In the third Project we proposed to examine the role of bacterial LPS (or LOS) receptors, CR3 and CD14, in the host response to genital infections with N. gonorrhoeae and C. trachomatis. We believe that innate immune responses determine the extent of uptake by both professional and non-professional phagocytes of these two pathogens. In the fourth Project we propose to examine the trafficking pathway of N. gonorrhoeae after it enters genital epithelial cells and the effects of the up-regulated asialoglycoprotein receptor in these events. Together with the third project we will also examine the basis upon which these cells produce cytokines in a CD14 independent fashion. In the fifth Project we propose to continue to investigate the immunologic hypothesis that women who resist infection with N. gonorrhoeae when exposed may have protective immunity. We will determine in vivo expression of and the immune response to a group of iron-regulated proteins in subjects with gonorrhea, examining also whether women who resist gonococcal infection harbor potentially protective immune responses. Together with the fourth Project, we will also examine the regulation of these proteins in the model of urethral epithelial cell infection.
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