Die Interaktion von pathogenen Neisserien mit Endothelzellen und ihre Rolle bei der Überwindung der Blut-Hirn-Schranke

脑膜炎奈瑟菌是一种革兰氏阴性微生物，专门生活在人类群体中，可能会患上一种致命的疾病--细菌性脑膜炎。这种病原体的特点是能够绕过宿主的杀菌机制，穿过血脑屏障感染中枢神经系统。作为先决条件，脑膜炎球菌必须与脑血管的内皮衬里相互作用才能进入脑膜。尽管已经确定了使这些细菌能够逃脱健康人类免疫防御的几个关键成分，但仍不清楚哪些因素使脑膜炎双球菌能够与内皮细胞层建立密切联系并通过内皮细胞层进行移位。通过这个项目，我们希望在分子水平上为了解脑膜炎奈瑟氏菌与内皮细胞的相互作用做出贡献。特别是，我们想要研究脑膜炎双球菌的毒力因子对内皮细胞的附着和侵袭以及通过内皮层的跨细胞作用。由于细菌性脑膜炎的发病过程也依赖于宿主成分的贡献，因此我们将研究感染内皮细胞对细胞内信号转导事件、基因表达以及与免疫系统循环细胞相互作用的能力的反应。这种结合的方法将使我们能够重建发生在病原体-内皮界面的事件序列，并将使我们能够指出这一过程的关键决定因素，这些因素可能对干预敏感。

Neisseria meningitidis, a gram-negative microorganism specialised to live within the human population, bears the potential for a deadly disease, bacterial meningitis. This pathogen is characterised by its ability to circumvent host bactericidal mechanisms and to cross the blood-brain barrier to infect the central nervous system. As a pre-requisite, meningococci have to interact with the endothelial lining of the brain vasculature to gain access to the meninges. Though several key components enabling these bacteria to escape the immune defence of healthy humans have been identified, it is still unclear which factors enable meningococci to establish tight contact with and to translocate through a layer of endothelial cells. With this project we would like to contribute to the understanding of N. meningitidis - endothelial cell interactions on the molecular level. In particular, we would like to investigate the meningococcal virulence factors contributing to attachment and invasion into endothelial cells and to the transcytosis through an endothelial layer. As the pathogenetic process of bacterial meningitis also depends on the contribution of host components, we will study the response of infected endothelial cells with regard to intracellular signal transduction events, gene expression, and ability to interact with circulating cells of the immune system. This combined approach will allow us to reconstruct the sequence of events occurring at the pathogen - endothelium interface and will enable us to point out key determinants of this process that could be sensitive to intervention.