Immunology of Infection with Neisseria gonorrhoeae

淋病奈瑟菌是大多数性传播疾病的两大病原体之一。 生殖器传播感染。补体构成先天免疫系统的一个重要方面， 对淋球菌感染的影响。我们实验室以前的工作表明，淋球菌的唾液酸化 脂低聚糖(LOS)通过结合宿主补体调节而导致补体抵抗 分子，因子H。孔蛋白分子也与因子H结合。 因子H的选择性剪接形式，称为因子H样分子1(FHL-1)在与 淋球菌和调节补体。某些淋病奈瑟氏菌株处理补体(即转换为 补充成分-3[C3b]到灭活形式[C3b])，并结合FHL-1，但不结合因子H辅因子 FHL-1的活性将使用只含FHL-1但不含完整因子H的血清进行评估，因为两者 因子H和FHL-1与细胞结合，我们将研究这两个分子在促进淋球菌感染中的作用 在第二个具体目标中，附着于永生化的宫颈和尿路上皮细胞，有三个问题 与洛杉矶分析有关的问题将得到解决。首先，H因子与淋球菌乳酸菌结合的特异性- 将检查N-新四糖(LNT)唾液酸，但不检查脑膜炎球菌LNT唾液酸。波林(波尔语) FH与淋球菌唾液酸结合的影响。我们将进行孔蛋白分子的等位基因交换 以考察孔蛋白对唾液酸化的LOS与H因子相互作用的影响 在基线上，这两个新系列物种之间存在差异。其次，我们将研究泛函的决定因素 脑膜炎双球菌和淋球菌异位基因转移酶的特异性 Ist基因在两个物种之间的交换。第三，我们还将确定为什么 血清敏感(高唾液酸摄取率)和血清稳定抵抗(低唾液酸摄取率)的唾液酸值不同 唾液酸摄取)淋球菌。这将通过检查~3H标记的CMP-NaNA的摄取来实现 同基因淋球菌仅在LST酶上有所不同。POR修改LST活动的可能性也将 在高唾液酸和低唾液酸之间进行POR基因的等位基因交换进行检查 发起人。在第三个具体目标中，我们将详细说明C4和C4之间的联系(酰胺和酯) LOS，LOS的己糖延伸对C4与LOS结合的影响，以及键的影响 在C4和LOS之间形成的杀菌作用。

Neisseria gonorrhoeae is one of the two major pathogens involved in the majority of cases of sexually transmitted genital infection. Complement forms an important aspect of the innate immune system that impacts upon gonococcal infection. Prior work in our laboratory has shown that sialylation of gonococcal lipooligosaccharide (LOS) results in complement resistance by binding the host complement regulatory molecule, factor H. The porin molecule also binds factor H. In the first Specific Aim, we will investigate the role of an alternatively-spliced version of factor H, called factor H-like molecule 1 (FHL-1)in binding to gonococci and in regulating complement. Some strains of N. gonorrhoeae process complement (i.e. convert complement component-3 [C3b] to the inactivated form [iC3b]) and bind FHL-1, but not factor H. Cofactor activity of FHL-1 will be assessed using serum containing only FHL-1, but not intact factor H. Because both factor H and FHL-1 bind to cells, we will examine the roles of these two molecules in facilitating gonococcal attachment to immortalized cervical and urethral epithelial cells, in the second Specific Aim, three questions that pertain to LOS sialylation will be addressed. First, the specificity of factor H binding to gonococcal lacto- N-neotetraose (LNT) sialic acid, but not to meningococcai LNT sialic acid, will be examined. Porin (Por) influences binding of fH to gonococcal sialic acid. We will perform allelic exchange of porin molecules between the two species to examine the effect of porin on the sialylated LOS interactions with factor H that differs at baseline in the two neisserial species. Second, we will examine the determinants of the functional specificity of the LOS sialyltransferase (IsO enzyme in meningococci and gonococci by performing allelic exchanges of the Ist genes between the two species. Third, we will also determine why the efficiency of LOS sialylation differs between serum-sensitive (high sialic acid uptake) and "stably" serum-resistant (low sialic acid uptake) gonococci. This will be performed by examining the uptake of 3H-labeled CMP-NANA by isogenic gonococci differing only in their Lst enzymes. The possibility that Por modifies Lst activity will also be examined by performing allelic exchanges of the Por genes between high and low sialic acid incorporators. In the third Specific Aim, we will detail the linkages (amide versus ester) between C4 and LOS, the effects of hexose extension of the LOS on binding of C4 to LOS, and the impact of the bond formed between C4 and LOS on bactericidal killing.