Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis.

Borrelia burgdorferi stimulation of chemokine secretion by cells of monocyte lineage in patients with Lyme arthritis.
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DOI:
10.1186/ar3128
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发表时间:
2010
影响因子:
4.9
通讯作者:
Steere AC
Steere AC
中科院分区:
医学2区
文献类型:
--
作者:
Shin JJ;Strle K;Glickstein LJ;Luster AD;Steere AC

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莱姆关节炎患者的关节液通常含有高水平的CCL 4和CCL 2,它们是单核细胞和一些T细胞的化学引诱物,以及CXCL 9和CXCL 10,它们是CD 4+和CD 8 + T效应细胞的化学引诱物。这些趋化因子主要由单核细胞谱系的细胞在TH 1型免疫应答中产生。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以多种方式刺激单核细胞/巨噬细胞分泌趋化因子,从而连接先天性和适应性免疫应答。用B刺激24例莱姆关节炎患者的外周血单个核细胞(PBMC)。在培养物上清液中测量感染的病原体、伯氏螺旋体、干扰素(IFN)-γ或两者的水平,以及CCL 4、CCL 2、CXCL 9和CXCL 10的水平。使用可用样品,以相同方式刺激来自PBMC和滑液单核细胞(SFMC)的CD 14+单核细胞/巨噬细胞。在来自PBMC和SFMC的T细胞上评估CXCL 9和CXCL 10的受体CXCR 3和CCL 4的受体CCR 5。在莱姆关节炎患者中,B。而IFN-γ则不能诱导PBMC分泌CCL 4和CCL 2,而B. Burgdorferi和IFN-γ各自刺激CXCL 9和CXCL 10的产生。然而,对于CD 14+细胞部分,B.单独的burgdorferi刺激CCL 4的分泌; B. IFN-γ单独刺激CXCL 9和CXCL 10的分泌。SFMC中表达CXCR 3或CCR 5的T细胞百分比显着高于PBMC,证实TH 1效应细胞被募集到炎症关节。然而,当用B. IFN-γ、SFMC和PBMC的反应相似。B。burgdorferi直接刺激PBMC或CD 14+单核细胞/巨噬细胞分泌CCL 4,但需要螺旋体刺激PBMC中存在的其他中间细胞以诱导CD 14+细胞分泌CCL 2、CXCL 9和CXCL 10。我们得出结论,B. burgdorferi直接和间接刺激单核细胞/巨噬细胞,以引导莱姆关节炎患者的先天性和适应性免疫应答。
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. 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. 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. 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.
DOI: 10.1189/jlb.0604356
发表时间: 2005-05-01
影响因子: 5.5
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发表时间: 2009-05
期刊: PLoS pathogens
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