Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis.

Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis.
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DOI:
10.1084/jem.20070962
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发表时间:
2008-01-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Fikrig E
Fikrig E
中科院分区:
其他
文献类型:
--
作者:
Pal U;Wang P;Bao F;Yang X;Samanta S;Schoen R;Wormser GP;Schwartz I;Fikrig E

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莱姆关节炎是由伯氏疏螺旋体在关节定植以及随之而来的宿主反应所导致。通过基于基因芯片的伯氏疏螺旋体基因表达差异分析以及定量逆转录 - 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。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和炎症。因此构建了缺失bmpA/B的伯氏疏螺旋体,以进一步探究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,并且不能诱发严重的关节炎。用bmpA和bmpB基因的野生型拷贝对突变螺旋体进行互补,部分恢复了原始表型。这些数据阐明了差异产生的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。
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.
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