Pal Utpal, Wang Penghua, Bao Fukai, Yang Xiuli, Samanta Swapna, Schoen Robert, Wormser Gary P, Schwartz Ira, Fikrig Erol
Section of Rheumatology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
J Exp Med. 2008 Jan 21;205(1):133-41. doi: 10.1084/jem.20070962. Epub 2007 Dec 31.
Lyme arthritis results from colonization of joints by Borrelia burgdorferi and the ensuing host response. Using gene array-based differential analysis of B. burgdorferi gene expression and quantitative reverse trancription-polymerase chain reaction, we identified two paralogous spirochete genes, bmpA and bmpB, that are preferentially up-regulated in mouse joints compared with other organs. Transfer of affinity-purified antibodies against either BmpA or BmpB into B. burgdorferi-infected mice selectively reduced spirochete numbers and inflammation in the joints. B. burgdorferi lacking bmpA/B were therefore generated to further explore the role of these proteins in the pathogenesis of Lyme disease. B. burgdorferi lacking bmpA/B were infectious in mice, but unable to persist in the joints, and they failed to induce severe arthritis. Complementation of the mutant spirochetes with a wild-type copy of the bmpA and bmpB genes partially restored the original phenotype. These data delineate a role for differentially produced B. burgdorferi antigens in spirochete colonization of mouse joints, and suggest new strategies for the treatment of Lyme arthritis.
莱姆关节炎是由伯氏疏螺旋体在关节中定植以及随后的宿主反应引起的。利用基于基因芯片的伯氏疏螺旋体基因表达差异分析和定量逆转录聚合酶链反应,我们鉴定出两个同源的螺旋体基因bmpA和bmpB,与其他器官相比,它们在小鼠关节中优先上调表达。将针对BmpA或BmpB的亲和纯化抗体转移到感染伯氏疏螺旋体的小鼠体内,可选择性地减少关节中的螺旋体数量并减轻炎症。因此,构建了缺失bmpA/B的伯氏疏螺旋体,以进一步探索这些蛋白质在莱姆病发病机制中的作用。缺失bmpA/B的伯氏疏螺旋体在小鼠中具有感染性,但无法在关节中持续存在,也未能诱发严重关节炎。用bmpA和bmpB基因的野生型拷贝对突变螺旋体进行互补,可部分恢复其原始表型。这些数据阐明了差异产生伯氏疏螺旋体抗原在小鼠关节螺旋体定植中的作用,并为莱姆关节炎的治疗提出了新策略。