ROLE OF LOS AND ITS RECEPTORS IN GONOCOCCAL PATHEGENEIS

描述(改编自申请人的摘要)：淋球菌是一种 性传播疾病的主要原因。而这种生物体主要是 感染下生殖道，它可以上升到上女性生殖器 肠道，某些菌株能够传播。世界上最早的事件 感染的建立涉及淋病奈瑟菌和淋球菌之间的相互作用。 存在于人类生殖道中的细胞。在这里，表面抗原在 淋球菌触发局部和全身体液免疫反应，从而导致 释放细胞因子、前列腺素和其他炎症介质。 以前的努力集中在确定对蛋白质的免疫反应上。 淋病奈瑟菌表面的抗原。相比之下，几乎没有人注意到 已经注意到了内毒素脂多糖的促炎作用， 覆盖在所有革兰氏阴性细菌的表面，包括 淋球菌。脑膜炎奈瑟菌，以及大多数肠道革兰氏阴性菌 病原体，很明显，急性细胞因子反应与 脓毒症综合症在很大程度上是由于内毒素与其相互作用所致。 感受器。然而，对于淋病奈瑟氏菌来说，它的内毒素(也称为 作为脂低聚糖或LOS)它们对不同菌株的反应性 淋球菌和它们的损失。这些都与上皮细胞的激活有关 在生殖道粘膜感染期间遇到的是未经证实的， 尽管其在体外的促炎活性已有文献记载。 这项提案的目标是描述淋球菌LOS在 淋病奈瑟菌与女性上皮细胞的相互作用 生殖道。首先，PI将表征三种新的上皮细胞 在细胞系方面，源自女性生殖道的细胞系可以 为研究淋球菌致病机制提供了一种新的体外模型 感染。第二，PI将在脂类A组分中产生两个突变体 淋球菌LOS。脂类A已被证明是导致 内毒素的促炎作用，以及脂类A的丢失或修饰 预计会影响革兰氏阴性细菌的致病性。最后， PI将检测上皮细胞受体对内毒素的作用 淋球菌的入侵和激活，重点是Toll，一个家族 受体是最近被发现的内毒素信号通路的组成部分。

Description (Adapted from the applicant's abstract): Neisseria gonorrhoeae is a major cause of sexually transmitted diseases. While this organism primarily infects the lower genital tract, it can ascend to the upper female genital tract, and certain strains are capable of dissemination. Early events in the establishment of infection involve interactions between N. gonorrhoeae and cells present in the human genital tract. Here, surface antigens on the gonococcus trigger the local and systemic humoral immune response that results in the release of cytokines, prostaglandins, and other inflammatory mediators. Previous efforts have focused on defining immunologic responses to protein antigens on the surface of N. gonorrhoeae. In contrast, little attention has been paid to the pro-inflammatory effects of the endotoxin lipopolysaccharide, LPS) that coats the surface of all Gram-negative bacteria, including the gonococcus. With Neisseria meningitidis, as well as most enteric Gram-negative pathogens, it is clear that the acute cytokine response associated with the sepsis syndrome is due, in a large part, to the interaction of LPS with its receptors. For N. gonorrhoeae, however, the role of its endotoxin (also known as lipooligosaccharide or LOS) their responsiveness to various strains of gonococci and their LOSs. These in the activation of epithelial cells encountered during mucosal infection of the genital tract are unproven, although its pro-inflammatory activity in vitro has been documented. The goal of this proposal is to characterize the role of gonococcal LOS in the interaction between N. gonorrhoeae and the epithelial cells found in the female genital tract. First, the PI will characterize three novel epithelial cell lines derived from the female genital tract in terms of cell lines may represent a new in vitro model for examining the pathogenesis of gonococcal infections. Second, the PI will make two mutants in the lipid A component of gonococcal LOS. Lipid A has been shown to be responsible for the pro-inflammatory effects of LPS, and loss or modification of lipid A would be expected to impact o the pathogenicity of a Gram-negative bacterium. Finally, the PI will examine the role of epithelial cell receptors for endotoxin in gonococcal invasion and activation, with an emphasis on Toll, a family of receptors recently identified as components of the LPS signaling pathway.