Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, A2209 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232, USA.
Vanderbilt Tuberculosis Center, Vanderbilt University Medical Center, A2209 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232, USA.
BMC Infect Dis. 2019 Apr 30;19(1):366. doi: 10.1186/s12879-019-3958-7.
Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1β), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1β in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent M. tuberculosis infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease.
Macrophages were stimulated with TLR-2 agonist M. tuberculosis lipoprotein (LpqH), live and gamma-irradiated M. tuberculosis.
M. tuberculosis - infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status; P = 0.02). Macrophages from persons with previous EPTB had a 38.88 μg/mL increase in median IL-1β production after stimulation with LpqH compared to uninfected contacts (P = 0.01); the effect was similar (44.99 μg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups.
There was increased macrophage expression of VDR after stimulation with live M. tuberculosis in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB.
在感染 HIV 之外，女性、黑种人或外国出生的人、维生素 D 受体 (VDR)、白细胞介素-1β (IL-1β) 和 Toll 样受体 (TLR)-2 中的遗传变异会增加肺外结核病 (EPTB) 的风险；功能相关性尚不清楚。我们评估了 HIV 血清阴性、既往 EPTB、既往肺结核、潜伏性结核分枝杆菌感染和未感染结核接触者的巨噬细胞中 VDR、TLR2、抗菌肽和 TNF-α 的表达，以及 IL-1β 的产生。由于疾病部位的免疫反应增强，先前有胸腔结核的人被排除在外。
用 TLR-2 激动剂结核分枝杆菌脂蛋白 (LpqH)、活的和伽马照射的结核分枝杆菌刺激巨噬细胞。
与未感染的接触者相比，既往 EPTB 患者感染的巨噬细胞中 VDR 表达增加（中位表达值增加 29.17 个相对值单位，经校正为外国出生状况后；P=0.02）。与未感染的接触者相比，用 LpqH 刺激后，既往 EPTB 患者的巨噬细胞中 IL-1β 的中位产量增加了 38.88μg/mL（P=0.01）；在控制外国出生状况后，效果相似（44.99μg/mL）但无统计学意义。中位 25-羟维生素 D 水平较低，但各组间无显著差异。
在既往肺外结核病患者中，用活结核分枝杆菌刺激后，巨噬细胞中 VDR 的表达增加。如果治疗后 VDR 的表达反映了疾病发生前的表达，则它可能会识别出患有肺外结核病的高危人群。
