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的侵袭起着关键作用，被认为是软脑膜强烈炎症的先决条件。我们之前使用人脑毛细血管内皮细胞(HBMEC)作为体外培养模型的工作表明，三因素相互作用对于HBEMC摄取脑膜炎球菌和通过血脑屏障是必不可少的：内化取决于粘附素OPC的表达，并包括纤维连接蛋白作为人血清衍生的内化促进因子，将脑膜炎球菌锚定到细胞(E1)上的特定整合素受体(a5b1整合素)。这些复杂相互作用的分子效应尚不清楚。表征配体-受体的相互作用以及随后诱导脑内皮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的血脑屏障内皮细胞中的事件。这些研究将有助于进一步了解脑膜炎双球菌入侵血脑屏障的分子机制，并为开发预防和治疗脑膜炎双球菌脑膜炎的新的治疗靶分子奠定基础。

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.