PATHOGENESIS OF NEISSERIA GONORRHOEAE IN A FEMALE MOUSE MODEL OF INFECTION

这个项目的主要目标是开发一种雌性小鼠模型 用于研究淋球菌(GC)对女性生殖的致病作用 用于评估GC疫苗。在第一个阶段取得的成果 这项为期五个月的项目包括成功地将老鼠移居 在发情期。阴道和子宫定植均为24例 接种后数小时，建议传播到上层 生殖道已经出现。感染持续时间较长的是 可能受到正常宿主因子变化的抑制，这些变化发生在 过渡到生殖周期的间情期。未来 因此，实验将使用雌激素治疗的小鼠来增加 易受感染。一旦这一模式标准化，免疫力 将通过挑战已康复的小鼠来研究感染 感染后，我们将探索保护性免疫反应的性质。 将特别强调在体内表达，和 根据流行病学数据，对GC不透明蛋白的免疫反应 这表明对这些蛋白质的抗体的存在减少了 患输卵管炎的风险。用纯化的GC免疫小鼠 蛋白质，然后挑战看看保护性抗原是否可以 已确定的，包括那些可能无法防止殖民的国家， 但要防止扩散到上生殖道。

The primary objective of this project is to develop an female mouse model for studying gonococcal (GC) pathogenesis of the female reproductive tract, and for evaluating 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, 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 reproductive tract.