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25(OH)D(3) 影响牛型分枝杆菌刺激的小鼠骨髓来源树突状细胞的成熟和功能。

25(OH)D(3) affects the maturation and function of mouse bone marrow-derived dendritic cells stimulated by Mycobacterium bovis BCG.

机构信息

Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, People's Republic of China.

出版信息

PLoS One. 2012;7(11):e48062. doi: 10.1371/journal.pone.0048062. Epub 2012 Nov 5.

Abstract

It has been shown that vitamin D deficiency increases an individual's susceptibility to tuberculosis (TB). However, very little is known about the effect of vitamin D on the immune response to Mycobacterium tuberculosis (M. tb) in dendritic cells (DCs). Because DCs play an important role in TB infection, we investigated the phenotypic characteristics and functional capabilities of mouse bone marrow-derived dendritic cells (BMDCs) after stimulation with Bacillus Calmette-Guérin (BCG) in the presence or absence of 25(OH)D(3)(100 nM). Bone marrow cells from mice were cultured with GM-CSF (20 ng/ml) and were then treated with 25(OH)D(3) for 7 days. On day 6, 5 µg/ml of BCG (≥1.0×10(6) CFU/mg) was added to the cells for 24 hours, and on day 7, the non-adherent cells were harvested for phenotypic and functional analyses. After incubation with 25(OH)D(3), the expression levels of MHC-II and CD86 on the surface of the dendritic cells (DCs) and the ability of the DCs to stimulate proliferation of allogeneic mixed lymphocytes were lower than control cells (p<0.05). Furthermore, the level of Interleukin (IL) -4 secreted by the BMDCs in the 25(OH)D(3) culture was lower than that in the control culture (p<0.01). However, the BMDCs cultured with 25(OH)D(3) produced significantly higher levels of IL-2, IL-6, IL-10 and interferon gamma(IFN-γ) than those in the control culture (p<0.05). These findings suggest that 25(OH)D(3) modulates the immune response during mycobacterial infection by affecting the maturation and function of DCs.

摘要

研究表明,维生素 D 缺乏会增加个体患结核病(TB)的易感性。然而,人们对维生素 D 对树突状细胞(DC)中结核分枝杆菌(M. tb)免疫反应的影响知之甚少。由于 DC 在 TB 感染中发挥重要作用,我们研究了在存在或不存在 25(OH)D(3)(100 nM)的情况下,用卡介苗(BCG)刺激后,小鼠骨髓来源的树突状细胞(BMDCs)的表型特征和功能能力。用 GM-CSF(20 ng/ml)培养来自小鼠的骨髓细胞,然后用 25(OH)D(3)处理 7 天。第 6 天,向细胞中加入 5 µg/ml 的 BCG(≥1.0×10(6)CFU/mg)24 小时,第 7 天收获非贴壁细胞进行表型和功能分析。与 25(OH)D(3)孵育后,树突状细胞(DC)表面 MHC-II 和 CD86 的表达水平以及 DC 刺激同种异体混合淋巴细胞增殖的能力均低于对照细胞(p<0.05)。此外,25(OH)D(3)培养的 BMDCs 分泌的白细胞介素(IL)-4 水平低于对照培养物(p<0.01)。然而,用 25(OH)D(3)培养的 BMDCs 产生的 IL-2、IL-6、IL-10 和干扰素γ(IFN-γ)水平明显高于对照培养物(p<0.05)。这些发现表明,25(OH)D(3)通过影响 DC 的成熟和功能来调节分枝杆菌感染期间的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cdc/3489893/78e3ced29798/pone.0048062.g001.jpg

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