ROLE OF LOS AND ITS RECEPTORS IN GONOCOCCAL PATHEGENEIS

描述（改编自申请人摘要）：淋病奈瑟菌是一种 性传播疾病的主要原因。虽然这种生物主要 感染下生殖道，它可以上升到上女性生殖器 道，并且某些菌株能够传播。早期事件 感染建立涉及N.淋病和 存在于人类生殖道中的细胞。在这里，表面抗原在 淋球菌引发局部和全身体液免疫反应， 释放细胞因子、胰高血糖素和其他炎症介质。 以前的努力集中在定义对蛋白质的免疫反应 N.淋病相比之下， 内毒素脂多糖的促炎作用， LPS），其覆盖所有革兰氏阴性细菌的表面，包括革兰氏阴性细菌。 淋球菌脑膜炎奈瑟菌，以及大多数肠道革兰氏阴性 病原体，很明显，急性细胞因子反应与 脓毒症综合征在很大程度上是由于LPS与其 受体。奈瑟氏菌的淋病，然而，其内毒素（也称为 作为脂寡糖或LOS）它们对各种菌株的反应性， 淋球菌及其丢失这些在上皮细胞的激活中 在生殖道粘膜感染过程中遇到的感染是未经证实的， 尽管其在体外的促炎活性已被证明。 这项建议的目的是描述淋球菌LOS在 N之间的相互作用淋病和在女性中发现的上皮细胞 生殖道首先，PI将表征三种新的上皮细胞 就细胞系而言，源自女性生殖道的细胞系可能 代表了一种新的体外模型，用于检查淋球菌的发病机制， 感染.第二，PI将在脂质A组分中产生两个突变体， 淋球菌LOS脂质A已被证明是负责 LPS的促炎作用，以及脂质A的损失或修饰将是 预期影响革兰氏阴性菌的致病性。最后， PI将检查上皮细胞内毒素受体在 淋球菌入侵和激活，重点是Toll，一个家族， 受体最近被确定为LPS信号通路的组分。

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.