Contribution of macrophages to Neisseria gonorrhoeae pathogenesis

项目2 -摘要 本研究提出的工作旨在研究奈瑟氏菌在巨噬细胞定植中的作用 淋病（N.g）在感染和淋病发展的影响。因为N.g是一个高度人性化的 适应病原体，它已经发展了许多机制，以避免和积极抑制先天和适应性 免疫反应。巨噬细胞大量存在于整个泌尿生殖道粘膜中， 约占从这些组织中回收的白细胞总数的10%。因此，很可能N.g 在感染期间遇到这些细胞，并且巨噬细胞在N.g发病机制中起重要作用。我们 发现N.g在巨噬细胞中定殖并建立拓扑上不同的集落。在殖民时期 神经元操纵肌动蛋白细胞骨架，创造一个支持细菌复制的细胞内小生境。这 巨噬细胞中N.g持续存在的新模型对淋病流行病学和结果具有重要意义，因为 在体内感染期间细菌的相关细胞贮库还有待鉴定。所以我们 假设N.g定殖并改变巨噬细胞免疫应答，以建立持续的 在宿主体内生长。在这个提议的第一个目标中，我们将研究在转录水平上发生的转录变化。 在巨噬细胞的N.g定殖期间，感染的细胞和细菌。在第二个目标中，我们将评估 巨噬细胞的存在和功能的小鼠模型中的N.g感染。

Project 2 - ABSTRACT The work proposed in this study seeks to investigate the role of macrophages colonization by Neisseria gonorrhoeae (N.g) during infection and the impact on gonorrhea development. Because N.g is a highly human adapted pathogen, it has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. Macrophages are present in significant numbers throughout the genitourinary mucosae and represent about 10% of total number of leukocytes recovered from these tissues. Thus, it’s likely that N.g encounters these cells during infection and that macrophages play an important role in N.g pathogenesis. We uncovered that N.g colonizes and establishes topologically distinct colonies in macrophages. During colonization N.g manipulates the actin cytoskeleton to create an intracellular niche supportive of bacterial replication. This new model of N.g persistence in macrophages is significant for gonorrhea symptomatology and outcome, since the relevant cellular reservoir of bacteria during in vivo infections has yet to be identified. Therefore, we hypothesize that N.g colonizes and alters the macrophages immune response in order to establish persistent growth within its host. In the first aim of this proposal we will investigate the transcriptional changes that occur in the infected cell and the bacterium during N.g colonization of macrophages. In the second aim we will assess the presence and the function of macrophages in a mouse model of N.g infection.