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细菌性脑膜炎是一种致死率极高的可怕疾病，症状出现后只需几个小时就可夺走患者的生命。英国诺丁汉大学科学家经过多年研究，终于发现脑膜炎细菌冲破人体天然防御机制并攻击大脑的机制。此发现有可能导致更有效的脑膜炎疗法和疫苗。 儿童期的细菌性脑膜炎几乎完全是由呼吸道病原体肺炎链球菌、脑膜炎奈瑟菌和流感嗜血杆菌引起的，但这些致命细菌如何冲破血脑屏障（BBB）的机制一直未被了解。 由诺丁汉大学临床微生物学教授德劳尔·艾拉艾尔丁领导的一个研究小组最近发现，所有的这三个病原体都以人脑血管内皮细胞（保护人体大脑免受疾病的特殊过滤系统）上的相同受体为目标，从而使生物体越过了血脑屏障。 这项发表在5月13日《临床研究杂志》上的研究结果表明，将细菌与受体相黏附的交互作用加以中断或调整，可为预防细菌性脑膜炎提供意想不到的广泛保护，同时提供了一个预防和治疗该疾病的靶标。 艾拉艾尔丁教授表示，此项发现是一个重大突破，将有助于设计出预防和治疗细菌性脑膜炎的新策略。人类受体与细菌配体的确定，就像是为一把锁找到了神秘的钥匙，这将打开一扇新的大门，并为新的发现铺平道路。 推荐原始出处： J. Clin. Invest. doi:10.1172/JCI36759. Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models Carlos J. Orihuela1, Jafar Mahdavi2, Justin Thornton1, Beth Mann1, Karl G. Wooldridge2, Noha Abouseada2, Neil J. Oldfield2, Tim Self3, Dlawer A.A. Ala’Aldeen2 and Elaine I. Tuomanen1 1Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA. 2Molecular Bacteriology and Immunology Group, Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, and 3Institute of Cell Signaling, University of Nottingham, Nottingham, United Kingdom. A diverse array of infectious agents, including prions and certain neurotropic viruses, bind to the laminin receptor (LR), and this determines tropism to the CNS. Bacterial meningitis in childhood is almost exclusively caused by the respiratory tract pathogens Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, but the mechanism by which they initiate contact with the vascular endothelium of the blood brain barrier (BBB) is unknown. We hypothesized that an interaction with LR might underlie their CNS tropism. Using affinity chromatography, coimmunoprecipitation, retagging, and in vivo imaging approaches, we identified 37/67-kDa LR as a common receptor for all 3 bacteria on the surface of rodent and human brain microvascular endothelial cells. Mutagenesis studies indicated that the corresponding bacterial LR-binding adhesins were pneumococcal CbpA, meningococcal PilQ and PorA, and OmpP2 of H. influenzae. The results of competitive binding experiments suggest that a common adhesin recognition site is present in the carboxyl terminus of LR. Together, these findings suggest that disruption or modulation of the interaction of bacterial adhesins with LR might engender unexpectedly broad protection against bacterial meningitis and may provide a therapeutic target for the prevention and treatment of disease. (责任编辑：Doctor001) |
