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酰化胆固醇半乳糖苷作为狭义伯氏疏螺旋体中的一种新型免疫原性基序。

Acylated cholesteryl galactoside as a novel immunogenic motif in Borrelia burgdorferi sensu stricto.

作者信息

Schröder Nicolas W J, Schombel Ursula, Heine Holger, Göbel Ulf B, Zähringer Ulrich, Schumann Ralf R

机构信息

Institut für Mikrobiologie und Hygiene, Universitätsklinikum Charité, Medizinische Fakultät der Humboldt-Universität zu Berlin, Dorotheenstrasse 96, D-10117 Berlin, Germany.

出版信息

J Biol Chem. 2003 Sep 5;278(36):33645-53. doi: 10.1074/jbc.M305799200. Epub 2003 Jun 16.

Abstract

Borrelia burgdorferi sensu lato is the causing agent of Lyme disease, an infectious disease frequently occurring in the United States, Europe, and Northern Asia. Currently, diagnosis of and vaccination strategies against this pathogen are exclusively based on proteinaceous structures. Here we report on a novel class of immunogenic glycolipids purified from B. burgdorferi sensu stricto B31. Employing a butanol/water extraction procedure with subsequent Bligh/Dyer extraction of the organic phase, thin layer chromatography analysis revealed the presence of three distinct glycolipids, which were chemically analyzed employing combined gas-liquid chromatography/mass spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry, and NMR. We identified acylated cholesteryl galactoside (ACG) next to cholesteryl galactoside and alpha-monogalactosyl-diacylglycerol. After extensive purification, the glycolipids investigated failed to cause proinflammatory responses in human cells transfected with human toll-like receptor (TLR)-2 or -4. However, we observed a marked recognition of ACG by sera derived from patients suffering from Lyme disease. These data indicate that newly described ACG is involved in developing host immunity during Lyme disease and thus may be useful for diagnosis and vaccination.

摘要

伯氏疏螺旋体狭义种是莱姆病的致病因子,莱姆病是一种在美国、欧洲和北亚频繁出现的传染病。目前,针对这种病原体的诊断和疫苗接种策略完全基于蛋白质结构。在此,我们报告了一类从狭义伯氏疏螺旋体B31中纯化出的新型免疫原性糖脂。采用丁醇/水提取程序,随后对有机相进行布利/戴尔提取,薄层色谱分析显示存在三种不同的糖脂,采用气相色谱/质谱联用、基质辅助激光解吸/电离质谱和核磁共振对其进行了化学分析。我们鉴定出除了胆固醇半乳糖苷和α-单半乳糖基二酰基甘油外,还有酰化胆固醇半乳糖苷(ACG)。经过广泛纯化后,所研究的糖脂未能在转染了人类 Toll 样受体(TLR)-2 或 -4 的人类细胞中引发促炎反应。然而,我们观察到莱姆病患者的血清对ACG有明显的识别作用。这些数据表明,新描述的ACG在莱姆病期间宿主免疫的发展中起作用,因此可能对诊断和疫苗接种有用。

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