Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis
Exposure to Candida albicans Polarizes a T-Cell Driven Arthritis Model towards Th17 Responses, Resulting in a More Destructive Arthritis
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DOI：
10.1371/journal.pone.0038889
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发表时间：
2012-06-12
期刊：
影响因子：
3.7
通讯作者：
van den Berg, Wim B.
中科院分区：
文献类型：
--
作者：
Marijnissen, Renoud J.;Koenders, Marije I.;van den Berg, Wim B.
背景：真菌成分已被证明在产生 Th17 反应方面非常有效。我们研究了关节炎关节中暴露于微量白色念珠菌是否改变了局部细胞因子环境，导致 Th17 扩增增强并导致更具破坏性的关节炎。 方法：通过将化脓性链球菌 (SCW) 细胞壁碎片重复注射到 C57Bl/6 小鼠的膝关节中，单独或与白色念珠菌或酵母聚糖 A 联合注射，诱导慢性 SCW 关节炎。对关节进行细胞因子水平、mRNA 表达和组织病理学分析。为了研究产生 IL-17 的 T 细胞的表型，分离了滑膜细胞并通过流式细胞术进行分析。 主要发现：与正常 SCW 组相比，在 SCW 注射之上关节内注射 Zymosan A 或 C. albicans 都会导致关节肿胀和炎症增强。然而，仅在SCW关节炎期间添加白色念珠菌就会导致严重的软骨细胞死亡并加剧软骨和骨的破坏。此外，暴露于白色念珠菌会导致关节炎关节中 IL-17 增加，同时伴有滑膜 T-bet 和 ROR gamma T mRNA 表达增加。此外，注射白色念珠菌的小鼠滑膜中的 Th17 细胞显着增多，其中大量细胞还产生 IFN-γ。结论：这项研究清楚地表明，微量的真菌成分（如白色念珠菌）在抑制炎症方面非常有效。干扰关节炎关节中的局部细胞因子环境，从而使关节炎极化为更具破坏性的表型。
Background: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis.Methodology: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW) cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry.Principal Findings: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and ROR gamma T. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-gamma.Conclusion: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype.