Gonococcal modulation of host immune responses during single and dual infections

淋病奈瑟菌和沙眼衣原体是两种最常见的 性传播的病原体N.淋病依赖于许多， 高度适应的宿主-病原体相互作用在人类泌尿生殖道中持续存在。 尿道或子宫颈的单纯性淋球菌感染导致有限的，非- 保护性的适应性免疫反应探讨了N.淋病 逃避宿主免疫被认为包括抗原变异和活性 感染细菌对免疫系统信号的操纵。我们的初步数据 证明了N.淋病抑制抗原呈递细胞的能力， 刺激CD 4 + T淋巴细胞增殖。N.淋病通过 外膜囊泡和无水肽聚糖片段的脱落 它的细胞壁 一些C。沙眼感染者似乎会产生保护性免疫 与感染有关在动物模型中，CD 4 + T淋巴细胞定向于衣原体， 抗原可以介导衣原体感染的保护性免疫。我们的初步数据 提出N.淋球菌能够交叉抑制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 信号传导机制和免疫反应的后果， N.淋病菌。进一步我们将确定N.淋病介导 免疫抑制在两种N.淋病感染和N.淋病/衣原体 共感染。

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.