SEXUALLY TRANSMITTED DISEASES COOPERATIVE RESEARCH CENTE

这一STD-CRC的主要目标是在自然环境中预防和控制两种主要的STD病原体--沙眼衣原体和淋病奈瑟菌--感染这些微生物的患者。提出了五个研究项目和四个服务中心(行政、临床、实验室和统计)。在第一个项目中，我们建议开发和评估一种教育干预措施，利用波士顿两家青少年诊所(波士顿医学中心和儿童医院)的人口，在性活跃的市中心青年中预防衣原体感染。在第二个项目中，我们建议使用新开发的基因技术来识别新的毒力基因和机制，特别是关注沙眼衣原体如何调节其二态生命周期。在第三个项目中，我们建议研究细菌内毒素(或LOS)受体CR3和CD14在淋球菌和沙眼衣原体生殖器感染宿主反应中的作用。我们认为，先天免疫反应决定了专业和非专业吞噬细胞对这两种病原体的摄取程度。在第四个项目中，我们建议研究淋球菌进入生殖器上皮细胞后的传播途径，以及上调的去唾液酸糖蛋白受体在这些事件中的作用。与第三个项目一起，我们还将研究这些细胞以CD14独立的方式产生细胞因子的基础。在第五个项目中，我们建议继续调查免疫学假说，即在暴露时抵抗淋病奈瑟菌感染的女性可能具有保护性免疫。我们将确定淋病患者体内一组铁调节蛋白的表达和免疫反应，并检查抵抗淋球菌感染的女性是否具有潜在的保护性免疫反应。与第四个项目一起，我们还将研究这些蛋白在尿路上皮细胞感染模型中的调节。

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.