Interaction of Neisseria meningitidis with cells of the human blood brain barrier

脑膜炎奈瑟菌与血脑屏障细胞的相互作用对脑脊液（CSF）的侵袭起着关键作用，被认为是轻脑膜强烈炎症的先决条件。我们之前的工作使用来自人脑毛细血管的内皮细胞（HBMEC）作为体外培养模型，证明了三因子相互作用对于脑膜炎球菌被HBMEC摄取和通过血脑屏障是必不可少的：内化依赖于粘附素Opc的表达，包括纤维连接蛋白作为一种人类血清衍生的内化促进因子，该因子将脑膜炎球菌锚定在细胞上的特定间素受体（a5b1整合素）上（E1）。这些复杂相互作用的分子效应仍然是未知的。脑内皮细胞中配体-受体相互作用的表征以及随后诱导的细胞内信号级联和基因表达将是我们未来工作的主要目标。脑膜炎奈瑟菌对宿主信号通路的操纵可能揭示宿主定植的基础，并阐明导致严重疾病状况的血脑屏障内皮细胞事件。这些研究将进一步有助于对脑膜炎球菌入侵血脑屏障的分子认识，并为开发新的预防和治疗脑膜炎球菌性脑膜炎的治疗靶点分子奠定基础。

The interaction of N. meningitidis with cells of the blood-brain barrier plays a pivotal role for invasion of the cerebrospinal fluid (CSF) and is thought to be the prerequisite for the strong inflammation of the leptomeninges. Our previous work using endothelial cells from human brain capillaries (HBMEC) as an in vitro culture model demonstrated that a trifactorial interaction is essential for uptake of meningococci by HBEMC and passage through the blood-brain barrier: the internalisation depends on the expression of the adhesin Opc and includes fibronectin as a human serum derived internalisation promoting factor which anchors the meningococcus to a specific intergrin receptor (a5b1 integrin) on the cell (E1). The molecular effects of these complex interactions are still unknown. The characterization of the ligand-receptor interaction and the subsequent induction of intracellular signalling cascades and gene expression in the cerebral endothelial cell will be the major objective of our future work. The manipulation of host signalling pathways by Neisseria meningitidis may reveal the basis of host colonisation and elucidate the events in the endothelial cell of the blood brain barrier that lead to serious disease conditions. These investigations will further contribute to the molecular understanding of the invasion of the blood brain barrier by meningococci and form the basis for the development of new therapeutic target molecules for prophylaxis and therapy of meningococcal menigitis.