PATHOGENESIS OF NEISSERIA GONORRHOEAE IN A FEMALE MOUSE MODEL OF INFECTION

本项目的主要目标是建立一个雌性小鼠模型 用于研究女性生殖道淋球菌（GC）的发病机制， 道，并用于评估GC疫苗。 前五年取得的成果 这个项目的几个月包括成功的小鼠殖民地， 发情期 24小时内可见阴道和子宫定植 接种后，表明传播到上层生殖系统 道发生了。 较长的感染持续时间可能受到抑制 由正常宿主因子变化引起的， 生殖周期的发情间期。 未来的实验将 因此，使用雌二醇治疗的小鼠， 感染 一旦这个模型被标准化， 通过挑战从感染中恢复的小鼠进行研究， 保护性免疫反应的性质将被探索。 特定 重点将放在体内表达和免疫 反应，GC不透明蛋白，基于流行病学数据， 表明这些蛋白的抗体的存在降低了 输卵管炎的风险。 将用纯化的GC蛋白免疫小鼠 然后进行挑战以观察是否可以识别保护性抗原， 包括那些可能不会防止殖民化，但保护 防止传播到上生殖道。

The primary objective of this project is to develop a female mouse model for studying gonococcal (GC) pathogenesis of the female reproductive tract, and for evluating GC vaccines. Results obtained in the first five months of this project include the successful colonization of mice in the estrus phase. Both vaginal and uterine colonization were seen 24 hours post inoculation, suggesting dissemination to the upper reproductive tract had occurred. Longer duration of infection was perhaps inhibited by normal host factor changes which occur upon transition into the diestrus phase of the reproductive cycle. Future experiments will therefore use estradiol-treated mice to increase susceptibility to infection. Once this model is standardized, immunity to infection will be studied by challenging mice who have recovered from infection, and the nature of the protective immune response will be explored. A particular emphasis will be placed on the in vivo expression of, and immune responses to, GC opacity proteins, based on epidemiological data which suggest that the presence of antibody to these proteins decreases the risk of salpingitis. Mice will be immunized with purified GC proteins and then challenged to see if protective antigens can be identified, including those that might not protect against colonization, but protect against dissemination to the upper reporductive tract.