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細(xì)菌性腦膜炎是一種致死率極高的可怕疾病，癥狀出現(xiàn)后只需幾個小時就可奪走患者的生命。英國諾丁漢大學(xué)科學(xué)家經(jīng)過多年研究，終于發(fā)現(xiàn)腦膜炎細(xì)菌沖破人體天然防御機制并攻擊大腦的機制。此發(fā)現(xiàn)有可能導(dǎo)致更有效的腦膜炎療法和疫苗。 兒童期的細(xì)菌性腦膜炎幾乎完全是由呼吸道病原體肺炎鏈球菌、腦膜炎奈瑟菌和流感嗜血桿菌引起的，但這些致命細(xì)菌如何沖破血腦屏障（BBB）的機制一直未被了解。 由諾丁漢大學(xué)臨床微生物學(xué)教授德勞爾·艾拉艾爾丁領(lǐng)導(dǎo)的一個研究小組最近發(fā)現(xiàn)，所有的這三個病原體都以人腦血管內(nèi)皮細(xì)胞（保護人體大腦免受疾病的特殊過濾系統(tǒng)）上的相同受體為目標(biāo)，從而使生物體越過了血腦屏障。 這項發(fā)表在5月13日《臨床研究雜志》上的研究結(jié)果表明，將細(xì)菌與受體相黏附的交互作用加以中斷或調(diào)整，可為預(yù)防細(xì)菌性腦膜炎提供意想不到的廣泛保護，同時提供了一個預(yù)防和治療該疾病的靶標(biāo)。 艾拉艾爾丁教授表示，此項發(fā)現(xiàn)是一個重大突破，將有助于設(shè)計出預(yù)防和治療細(xì)菌性腦膜炎的新策略。人類受體與細(xì)菌配體的確定，就像是為一把鎖找到了神秘的鑰匙，這將打開一扇新的大門，并為新的發(fā)現(xiàn)鋪平道路。 推薦原始出處： 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. (責(zé)任編輯：Doctor001) |
