Gonococcal modulation of host immune responses during single and dual infections

淋球菌和沙眼衣原体是最常见的两种 全世界最大的性传播病原体。淋病奈瑟菌依赖于数量众多， 高度适应宿主-病原体的相互作用以持续存在于人类泌尿生殖道。 尿路或宫颈的非复杂性淋球菌感染导致有限的和非 保护性、适应性免疫反应。淋病奈瑟菌的致病机制 逃避宿主免疫被认为既包括抗原变异也包括主动免疫 感染细菌对免疫系统信号的操纵。我们的初步数据 证明淋病奈瑟菌可抑制抗原提呈细胞 刺激CD4+T淋巴细胞增殖。淋病奈瑟菌通过 外膜囊泡和无水肽聚糖碎片的脱落 它的细胞壁。 一些沙眼衣原体感染者似乎产生了保护性免疫。 对感染的影响。在动物模型中，CD4+T淋巴细胞导向衣原体 在衣原体感染中，抗原可介导保护性免疫。我们的初步数据 提示淋病奈瑟菌能够交叉抑制T淋巴细胞增殖 针对衣原体抗原。在本提案中，我们建议确定 激活的免疫反应的信号机制和后果 淋病奈瑟菌。此外，我们将确定淋病奈瑟氏菌介导的影响。 淋球菌感染和淋病/衣原体的免疫抑制 混合感染。

Neisseria gonorrhoeae and Chlamydia trachomatis are two of the most common sexually transmitted pathogens in the world. N. gonorrhoeae depends on numerous, highly adapted host-pathogen interactions to persist in the human urogenital tract. Uncomplicated gonococcal infection of the urethra or cervix leads to limited, and non- protective, adaptive immune responses. The mechanisms by which N. gonorrhoeae evades host immunity are thought to include both antigenic variation and active manipulation of immune system signaling by the infecting bacteria. Our preliminary data demonstrates that N. gonorrhoeae inhibits the ability of antigen presenting cells to stimulate CD4+ T lymphocyte proliferation. N. gonorrhoeae accomplishes this through the shedding of outer membrane vesicles and anhydrous peptidoglycan fragments from its cell wall. Some C. trachomatis infected individuals appear to develop protective immunity to the infection. In animal models, CD4+ T lymphocytes directed towards chlamydial antigens can mediate protective immuniity in chlamydial infection. Our preliminary data suggest that N. gonorrhoeae is able to cross suppress T lymphocyte proliferation directed towards chlamydial antigens. In this proposal we propose to identify the signaling mechanisms and consequences to the immune response that are activated by N. gonorrheoeae. Further we will determine the impact of N. gonorrhoeae-mediated immune suppression in both N. gonorrhoeae infection and N. gonorrhoeae/Chlamydia co-infection.