Division of Rheumatology, Allergy and Immunology, the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Am J Pathol. 2011 Jun;178(6):2726-39. doi: 10.1016/j.ajpath.2011.02.018.
Evidence is emerging for differential pathogenicity among Borrelia burgdorferi genotypes in the United States. By using two linked genotyping systems, ribosomal RNA intergenic spacer type (RST) and outer surface protein C (OspC), we studied the inflammatory potential of B. burgdorferi genotypes in cells and patients with erythema migrans or Lyme arthritis. When macrophages were stimulated with 10 isolates of each RST1, RST2, or RST3 strain, RST1 (OspC type A)-stimulated cells expressed significantly higher levels of IL-6, IL-8, chemokine ligand (CCL) 3, CCL4, tumor necrosis factor, and IL-1β, factors associated with innate immune responses. In peripheral blood mononuclear cells, RST1 strains again stimulated significantly higher levels of these mediators. Moreover, compared with RST2, RST1 isolates induced significantly more interferon (IFN)-α, IFN-γ, and CXCL10, which are needed for adaptive immune responses; however, OspC type I (RST3) approached RST1 (OspC type A) in stimulating these adaptive immune mediators. Similarly, serum samples from patients with erythema migrans who were infected with the RST1 genotype had significantly higher levels of almost all of these mediators, including exceptionally high levels of IFN-γ-inducible chemokines, CCL2, CXCL9, and CXCL10; and this pronounced inflammatory response was associated with more symptomatic infection. Differences among genotypes were not as great in patients with Lyme arthritis, but those infected with RST1 strains more often had antibiotic-refractory arthritis. Thus, the B. burgdorferi RST1 (OspC type A) genotype, followed by the RST3 (OspC type I) genotype, causes greater inflammation and more severe disease, establishing a link between spirochetal virulence and host inflammation.
在美国，伯氏疏螺旋体基因型的致病性存在差异，这一证据逐渐浮现。我们使用两种连锁基因分型系统，核糖体 RNA 基因间区（RST）和外膜蛋白 C（OspC），研究了伯氏疏螺旋体基因型在细胞和患有游走性红斑或莱姆关节炎的患者中的炎症潜能。当巨噬细胞被 10 株每种 RST1、RST2 或 RST3 菌株的 RST 刺激时，RST1（OspC 型 A）刺激的细胞表达了明显更高水平的 IL-6、IL-8、趋化因子配体（CCL）3、CCL4、肿瘤坏死因子和 IL-1β，这些因子与先天免疫反应有关。在外周血单核细胞中，RST1 株再次刺激了明显更高水平的这些介质。此外，与 RST2 相比，RST1 分离株诱导了明显更高水平的 IFN-α、IFN-γ 和 CXCL10，这些都是适应性免疫反应所必需的；然而，OspC 型 I（RST3）在刺激这些适应性免疫介质方面接近 RST1（OspC 型 A）。同样，感染 RST1 基因型的游走性红斑患者的血清样本具有明显更高水平的几乎所有这些介质，包括 IFN-γ 诱导的趋化因子 CCL2、CXCL9 和 CXCL10 的异常高水平；这种明显的炎症反应与更具症状性的感染有关。在莱姆关节炎患者中，基因型之间的差异不那么大，但感染 RST1 株的患者更常发生抗生素难治性关节炎。因此，伯氏疏螺旋体 RST1（OspC 型 A）基因型，其次是 RST3（OspC 型 I）基因型，导致更大的炎症和更严重的疾病，在螺旋体毒力和宿主炎症之间建立了联系。
