Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, USA.
Mol Microbiol. 2013 Oct;90(2):241-51. doi: 10.1111/mmi.12377. Epub 2013 Sep 16.
The Lyme disease spirochaete, Borrelia burgdorferi, causes damage to diverse host tissues and induces inflammation but the mechanisms of injury are poorly understood. We recently reported that a surface-exposed B. burgdorferi protease, which is expressed during human disease and is conserved within the major Lyme disease spirochaete species, degrades the extracellular matrix proteoglycan, aggrecan. Here we demonstrate that BbHtrA also degrades fibronectin and numerous proteoglycans found in skin, joints and neural tissues. BbHtrA degradation of fibronectin released known pro-inflammatory fibronectin fragments FnIII(13-14) and Fnf-29, which may amplify the inflammatory processes triggered by the presence of the bacteria. When this hypothesis was tested directly by exposing chondrocytes to BbHtrA in vitro, inflammatory cytokines (sICAM-1 and IL-6) and chemokines (CXCL1, CCL1, CCL2 and CCL5) that are hallmarks of Lyme disease were induced. These results provide the first evidence that, by utilizing BbHtrA, B. burgdorferi may actively participate in its dissemination and in the tissue damage and inflammation observed in Lyme disease.
莱姆病螺旋体，伯氏疏螺旋体，会对多种宿主组织造成损伤并引发炎症，但损伤机制尚不清楚。我们最近报道，一种表面暴露的伯氏疏螺旋体蛋白酶，在人类疾病期间表达，并且在主要莱姆病螺旋体物种中保守，可降解细胞外基质蛋白聚糖，聚集蛋白聚糖。在这里，我们证明 BbHtrA 还可降解皮肤、关节和神经组织中发现的纤连蛋白和许多蛋白聚糖。BbHtrA 降解纤连蛋白释放出已知的促炎纤连蛋白片段 FnIII(13-14)和 Fnf-29，这可能放大由细菌存在引发的炎症过程。当通过在体外将软骨细胞暴露于 BbHtrA 直接检验这一假设时，诱导了莱姆病的标志性细胞因子（sICAM-1 和 IL-6）和趋化因子（CXCL1、CCL1、CCL2 和 CCL5）。这些结果首次提供了证据，表明伯氏疏螺旋体可能通过利用 BbHtrA 积极参与其传播以及莱姆病中观察到的组织损伤和炎症。
