SEXUALLY TRANSMITTED DISEASES COOPERATIVE RESEARCH CENTE

该STD- crc的主要目标是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，在其自然环境下感染这些生物体的患者。提出了5个研究项目和4个服务核心（行政、临床、实验室和统计）。在第一个项目中，我们建议利用波士顿两家青少年诊所（波士顿医疗中心和儿童医院）的人口，开发和评估一种教育干预措施，以预防性活跃的市中心青少年中的衣原体感染。在第二个项目中，我们建议使用新开发的遗传技术来鉴定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，我们提出研究细菌LPS（或LOS）受体CR3和CD14在宿主对淋病奈瑟菌和沙眼奈瑟菌生殖器感染的反应中的作用。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，我们将研究淋病奈瑟菌进入生殖器上皮细胞后的转运途径以及上调的asialglycoprotein受体在这些过程中的作用。与第三个项目一起，我们还将研究这些细胞以CD14独立方式产生细胞因子的基础。在第五个项目中，我们建议继续研究暴露后抵抗淋病奈瑟菌感染的妇女可能具有保护性免疫的免疫学假设。我们将确定淋病患者体内对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妇女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道上皮细胞感染模型中的调控。

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.