伯氏疏螺旋体刺激单核细胞系细胞分泌趋化因子在莱姆关节炎患者。
Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis.
机构信息
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
出版信息
Arthritis Res Ther. 2010;12(5):R168. doi: 10.1186/ar3128. Epub 2010 Sep 9.
INTRODUCTION
Joint fluid in patients with Lyme arthritis often contains high levels of CCL4 and CCL2, which are chemoattractants for monocytes and some T cells, and CXCL9 and CXCL10, which are chemoattractants for CD4+ and CD8+ T effector cells. These chemokines are produced primarily by cells of monocyte lineage in TH1-type immune responses. Our goal was to begin to learn how infection with Borrelia burgdorferi leads to the secretion of these chemokines, using patient cell samples. We hypothesized that B. burgdorferi stimulates chemokine secretion from monocytes/macrophages in multiple ways, thereby linking innate and adaptive immune responses.
METHODS
Peripheral blood mononuclear cells (PBMC) from 24 Lyme arthritis patients were stimulated with B. burgdorferi, interferon (IFN)-γ, or both, and the levels of CCL4, CCL2, CXCL9 and CXCL10 were measured in culture supernatants. CD14+ monocytes/macrophages from PBMC and synovial fluid mononuclear cells (SFMC) were stimulated in the same way, using available samples. CXCR3, the receptor for CXCL9 and CXCL10, and CCR5, the receptor for CCL4, were assessed on T cells from PBMC and SFMC.
RESULTS
In patients with Lyme arthritis, B. burgdorferi but not IFN-γ induced PBMC to secrete CCL4 and CCL2, and B. burgdorferi and IFN-γ each stimulated the production of CXCL9 and CXCL10. However, with the CD14+ cell fraction, B. burgdorferi alone stimulated the secretion of CCL4; B. burgdorferi and IFN-γ together induced CCL2 secretion, and IFN-γ alone stimulated the secretion of CXCL9 and CXCL10. The percentage of T cells expressing CXCR3 or CCR5 was significantly greater in SFMC than PBMC, confirming that TH1 effector cells were recruited to inflamed joints. However, when stimulated with B. burgdorferi or IFN-γ, SFMC and PBMC responded similarly.
CONCLUSIONS
B. burgdorferi stimulates PBMC or CD14+ monocytes/macrophages directly to secrete CCL4, but spirochetal stimulation of other intermediate cells, which are present in PBMC, is required to induce CD14+ cells to secrete CCL2, CXCL9 and CXCL10. We conclude that B. burgdorferi stimulates monocytes/macrophages directly and indirectly to guide innate and adaptive immune responses in patients with Lyme arthritis.
简介
莱姆关节炎患者的关节液中常含有高水平的 CCL4 和 CCL2，它们是单核细胞和一些 T 细胞的趋化因子，而 CXCL9 和 CXCL10 则是 CD4+和 CD8+T 效应细胞的趋化因子。这些趋化因子主要由 TH1 型免疫应答中的单核细胞谱系细胞产生。我们的目标是开始了解伯氏疏螺旋体感染如何导致这些趋化因子的分泌，使用患者的细胞样本。我们假设 B. burgdorferi 通过多种方式刺激单核细胞/巨噬细胞分泌趋化因子，从而将先天免疫和适应性免疫反应联系起来。
方法
用 B. burgdorferi、干扰素 (IFN)-γ 或两者同时刺激 24 例莱姆关节炎患者的外周血单核细胞 (PBMC)，并测量培养上清液中 CCL4、CCL2、CXCL9 和 CXCL10 的水平。用现有的样本，以同样的方式刺激 PBMC 和滑液单核细胞 (SFMC) 中的 CD14+单核细胞/巨噬细胞。评估 PBMC 和 SFMC 中的 T 细胞上的 CXCR3（CXCL9 和 CXCL10 的受体）和 CCR5（CCL4 的受体）。
结果
在莱姆关节炎患者中，B. burgdorferi 而非 IFN-γ 诱导 PBMC 分泌 CCL4 和 CCL2，B. burgdorferi 和 IFN-γ 均刺激 CXCL9 和 CXCL10 的产生。然而，对于 CD14+细胞部分，B. burgdorferi 单独刺激 CCL4 的分泌；B. burgdorferi 和 IFN-γ 共同诱导 CCL2 分泌，IFN-γ 单独刺激 CXCL9 和 CXCL10 的分泌。与 PBMC 相比，SFMC 中表达 CXCR3 或 CCR5 的 T 细胞百分比显著更高，这证实了 TH1 效应细胞被募集到发炎的关节。然而，当用 B. burgdorferi 或 IFN-γ 刺激时，SFMC 和 PBMC 的反应相似。
结论
B. burgdorferi 直接刺激 PBMC 或 CD14+单核细胞/巨噬细胞分泌 CCL4，但需要伯氏疏螺旋体刺激 PBMC 中存在的其他中间细胞，才能诱导 CD14+细胞分泌 CCL2、CXCL9 和 CXCL10。我们的结论是，B. burgdorferi 直接和间接刺激单核细胞/巨噬细胞，指导莱姆关节炎患者的先天免疫和适应性免疫反应。
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