Department of Orthopedics, General Hospital of Northern Theater Command, Shenyang, Liaoning 110015, P.R. China.
Mol Med Rep. 2019 Dec;20(6):5265-5271. doi: 10.3892/mmr.2019.10780. Epub 2019 Oct 30.
Vitamin D deficiency may lead to an increased risk of tuberculosis. In the present study, the effects of Mycobacterium tuberculosis (Mtb) infection on dendritic cells (DCs) derived from vitamin D‑deficient mice or normal control mice were investigated. A vitamin D‑deficient mouse model was established, and bone marrow‑derived DCs (BMDCs) were isolated and treated with GM‑CSF and interleukin (IL)‑4 for 6 days, followed by an additional 24 h of treatment with Bacillus Calmette‑Guérin (BCG). The expression levels of surface molecules of DCs, including integrin alpha‑X and T‑lymphocyte activation antigen CD86, were significantly increased by BCG in the vitamin D‑deficient mice model group compared with the control group, while those of T‑lymphocyte activation antigen CD80, major histocompatibility complex class I and major histocompatibility complex class II were significantly decreased. These changes were BCG concentration‑dependent. In addition, the levels of IL‑4, IL‑6 and IL‑10 in the BMDCs from the vitamin D‑deficient mice were significantly decreased compared with the control mice, while the levels of tumor necrosis factor‑α, IL‑5, IL‑2, IL‑12 and interferon‑γ were significantly increased. Furthermore, the expression levels of vitamin D receptor (VDR) and CYP27B1 protein in the BMDCs from the vitamin D‑deficient mice were decreased compared with the control. BCG significantly increased the expression levels of VDR and CYP27B1 in the BMDCs. The DCs treated with BCG significantly induced the viability of CD4+ T lymphocytes. Therefore, BCG increases DCs and may enhance immunofunction, which may assist in preventing the risk of tuberculosis in patients with a vitamin D deficiency.
维生素 D 缺乏可能导致结核病风险增加。在本研究中,研究了结核分枝杆菌 (Mtb) 感染对来自维生素 D 缺乏小鼠或正常对照小鼠的树突状细胞 (DC) 的影响。建立了维生素 D 缺乏小鼠模型,分离并培养骨髓来源的 DC (BMDC),用 GM-CSF 和白细胞介素 (IL)-4 处理 6 天,然后用卡介苗 (BCG) 再处理 24 小时。与对照组相比,维生素 D 缺乏小鼠模型组中 BCG 显著增加了 DC 表面分子整合素 alpha-X 和 T 淋巴细胞活化抗原 CD86 的表达水平,而 T 淋巴细胞活化抗原 CD80、主要组织相容性复合体 I 和主要组织相容性复合体 II 的表达水平显著降低。这些变化与 BCG 浓度有关。此外,与对照组相比,维生素 D 缺乏小鼠的 BMDC 中 IL-4、IL-6 和 IL-10 的水平显著降低,而肿瘤坏死因子-α、IL-5、IL-2、IL-12 和干扰素-γ的水平显著升高。此外,与对照组相比,维生素 D 缺乏小鼠的 BMDC 中维生素 D 受体 (VDR) 和 CYP27B1 蛋白的表达水平降低。BCG 显著增加了 BMDC 中 VDR 和 CYP27B1 的表达水平。用 BCG 处理的 DC 显著诱导 CD4+T 淋巴细胞的活力。因此,BCG 增加了 DC,并可能增强免疫功能,有助于预防维生素 D 缺乏症患者的结核病风险。