Hirschfeld M, Kirschning C J, Schwandner R, Wesche H, Weis J H, Wooten R M, Weis J J
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
J Immunol. 1999 Sep 1;163(5):2382-6.
The agent of Lyme disease, Borrelia burgdorferi, produces membrane lipoproteins possessing potent inflammatory properties linked to disease pathology. The recent association of toll-like receptors (TLR) 2 and 4 with LPS responses prompted the examination of TLR involvement in lipoprotein signaling. The ability of human cell lines to respond to lipoproteins was correlated with the expression of TLR2. Transfection of TLR2 into cell lines conferred responsiveness to lipoproteins, lipopeptides, and sonicated B. burgdorferi, as measured by nuclear translocation of NF-kappaB and cytokine production. The physiological importance of this interaction was demonstrated by the 10-fold greater sensitivity of TLR2-transfected cells to lipoproteins than LPS. Futhermore, TLR2-dependent signaling by lipoproteins was facilitated by CD14. These data indicate that TLR2 facilitates the inflammatory events associated with Lyme arthritis. In addition, the widespread expression of lipoproteins by other bacterial species suggests that this interaction may have broad implications in microbial inflammation and pathogenesis.
莱姆病的病原体伯氏疏螺旋体产生具有与疾病病理相关的强大炎症特性的膜脂蛋白。近期Toll样受体(TLR)2和4与脂多糖反应的关联促使人们研究TLR在脂蛋白信号传导中的作用。人类细胞系对脂蛋白的反应能力与TLR2的表达相关。将TLR2转染到细胞系中可赋予其对脂蛋白、脂肽和超声处理过的伯氏疏螺旋体的反应能力,这通过核因子κB的核转位和细胞因子产生来衡量。与脂多糖相比,转染了TLR2的细胞对脂蛋白的敏感性高10倍,这证明了这种相互作用的生理重要性。此外,CD14促进了脂蛋白依赖TLR2的信号传导。这些数据表明,TLR2促进了与莱姆关节炎相关的炎症事件。此外,其他细菌物种广泛表达脂蛋白表明这种相互作用可能在微生物炎症和发病机制中具有广泛影响。