Orchestration of Inflammation and Adaptive Immunity in Borrelia burgdorferi-Induced Arthritis by Neutrophil-Activating Protein A
Orchestration of Inflammation and Adaptive Immunity in Borrelia burgdorferi-Induced Arthritis by Neutrophil-Activating Protein A
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DOI：
10.1002/art.37875
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发表时间：
2013-05-01
影响因子：
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通讯作者：
de Bernard, Marina
中科院分区：
文献类型：
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作者：
Codolo, Gaia;Bossi, Fleur;de Bernard, Marina
目的莱姆关节炎（Lyme arthritis，LA）是一种以中性粒细胞（polymorphisms cell，PMNs）和T细胞为主的炎性细胞浸润为特征的疾病。本研究旨在评估伯氏疏螺旋体的嗜中性粒细胞活化蛋白A（NapA）在引发炎症和驱动适应性免疫反应中的作用。方法采用酶联免疫吸附法检测LA患者关节液中NapA、干扰素（IFN）、白细胞介素-17（IL-17）和T细胞趋化因子的水平。通过荧光激活细胞分选分析确定LA患者滑膜中募集的T细胞概况。将NapA关节内注射到大鼠膝关节中，并对滑膜中募集的细胞进行表征。NapA在募集免疫细胞中的作用通过使用Transwell系统的趋化性测定来证实。结果LA患者滑液中有NapA、IFN、IL-17、CCL 2、CCL 20和CXCL 10的蓄积。因此，从这些患者获得的T细胞产生IFN或IL-17，但值得注意的是，一些产生两种细胞因子。NapA促进中性粒细胞和T淋巴细胞募集在体外和体内。有趣的是，T细胞的浸润不仅是由于NapA的趋化活性，但也依赖于中性粒细胞暴露于NapA产生的趋化因子。结论NapA是LA发病的主要细菌产物之一。因此，我们发现，在LA的早期阶段，NapA积累，反过来，协调炎症细胞进入关节腔的招聘。此后，在募集细胞的贡献下，NapA促进产生IL-17和/或IFN的T细胞的浸润。
Objective Lyme arthritis (LA) is characterized by infiltration of inflammatory cells, mainly neutrophils (polymorphonuclear cells [PMNs]) and T cells, into the joints. This study was undertaken to evaluate the role of the neutrophil-activating protein A (NapA) of Borrelia burgdorferi in eliciting inflammation and in driving the adaptive immune response. Methods Levels of NapA, interferon- (IFN), interleukin-17 (IL-17), and T cellattracting chemokines were assessed by enzyme-linked immunosorbent assay in synovial fluid from patients with LA. The profile of T cells recruited into the synovia of patients with LA was defined by fluorescence-activated cell sorting analysis. NapA was intraarticularly injected into rat knees, and the cells recruited in synovia were characterized. The role of NapA in recruiting immune cells was confirmed by chemotaxis assays using a Transwell system. Results NapA, IFN, IL-17, CCL2, CCL20, and CXCL10 accumulated in synovial fluid from patients with LA. Accordingly, T cells obtained from these patients produced IFN or IL-17, but notably, some produced both cytokines. NapA promoted neutrophil and T lymphocyte recruitment both in vitro and in vivo. Interestingly, the infiltration of T cells not only resulted from the chemotactic activity of NapA but also relied on the chemokines produced by PMNs exposed to NapA. Conclusion We provide evidence that NapA functions as one of the main bacterial products involved in the pathogenesis of LA. Accordingly, we show that, at very early stages of LA, NapA accumulates and, in turn, orchestrates the recruitment of inflammatory cells into the joint cavity. Thereafter, with the contribution of recruited cells, NapA promotes the infiltration of T cells producing IL-17 and/or IFN.