The role of inflammasome signaling in the pathogenesis of gonococcal disease

淋球菌(淋球菌或GC)是中国最常见的性传播病原体之一。 整个世界。淋病奈瑟氏菌依赖于大量高度适应的宿主-病原体相互作用才能持续存在 人类的泌尿生殖道。局部淋球菌感染的特征通常是自相矛盾的 免疫学发现，包括局部炎症，但有限的和非保护性的适应性免疫 回应。同时，播散性淋病常常与粘膜有关。 淋球菌的定植未能刺激宿主炎症反应，而炎症反应是淋病的标志 局部感染。淋病奈瑟菌引起这种矛盾的宿主反应的机制是 认为既涉及抗原变异，也涉及免疫系统信号的主动操纵，由 感染细菌 男性淋球菌感染与包括IL-1在内的炎性细胞因子的产生有关。 伊贝塔。我们最近发现淋球菌通过激活宿主来诱导IL-1β的产生 病原体识别信号系统称为炎症体。炎症小体的激活也 导致最近发现的一种称为肾坏死的细胞死亡程序。与细胞凋亡不同，肾小球坏死是 一种促炎过程，导致细胞内内容物的释放，起到炎症的作用 调解人。淋球菌比共生奈瑟氏菌更有效地激活这一途径，并 这是通过向环境中释放因子来实现的，这表明该途径的激活 可能与淋病奈瑟菌的毒力有关。 淋球菌可能通过多种机制优先激活NLRP3信号 路径。在与几个SE STI CRC调查人员的合作下，我们提出了一系列研究 探讨参与该信号通路激活的宿主和病原体因素及其参与 淋病奈瑟菌的先天和获得性免疫反应

Neisseria gonorrhoeae (gonococcus or GC) is one 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. Localized gonococcal infection is often characterized by paradoxical immunologic findings that include localized inflammation but limited, and non-protective, adaptive immune responses. At the same time, disseminated gonococcal diseases are often associated with mucosal colonization by N. gonorrhoeae that fails to stimulate the host inflammatory response that is a hallmark of localized infections. The mechanisms by which N. gonorrhoeae induces this paradoxical host response are thought to involve both antigenic variation and active manipulation of immune system signaling by the infecting bacteria Gonococcal infection, in human men is associated with production of inflammatory cytokines, including IL-. Ibeta. We have recently found that N. gonorrhoeae induces IL-1 beta production by activation of a host pathogen recognition signaling system known as the inflammasome. Activation of the inflammasome also induces a recently identified program of cell death known as pyronecrosis. Unlike apoptosis, pyronecrosis is a proinflammatory process resulting in the release of intracellular contents which act as inflammatory mediators. The gonococcus activates this pathway more potently than commensal Neisseria species and does so through the the release of factors into the environment, suggesting that activation of the pathway may be related to virulence of N. gonorrhoeae. There are multiple mechanisms by which N. gonorrhoeae may preferentially activate the NLRP3 signaling pathway. In collaboration with several SE STI CRC investigators, we propose a series of studies to investigate the host and pathogen factors involved in activation of this signaling pathway and its involvement in innate and adaptive immune responses to N. gonorrhoeae