Knowledge Synthesis Inc., 725 Folger Avenue, Berkeley, CA 94710.
Public Health Research Institute and Department of Medicine, New Jersey Medical School, Rutgers University, Newark, NJ 07103.
J Immunol. 2014 Jul 1;193(1):30-34. doi: 10.4049/jimmunol.1400736. Epub 2014 Jun 4.
Vitamin D has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat because of multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. In this article, we report a novel, metabolic role for vitamin D in tuberculosis identified through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed an association between vitamin D receptor (VDR) and lipid metabolism in human tuberculosis and infected macrophages. Vitamin D treatment of infected macrophages abrogated infection-induced accumulation of lipid droplets, which are required for intracellular M. tuberculosis growth. Additional transcriptomics results showed that vitamin D downregulates the proadipogenic peroxisome proliferator-activated receptor γ (PPARγ) in infected macrophages. PPARγ agonists reversed the antiadipogenic and the antimicrobial effects of VDR, indicating a link between VDR and PPARγ signaling in regulating both vitamin D functions. These findings suggest the potential for host-based, adjunct antituberculosis therapy targeting lipid metabolism.
维生素 D 长期以来一直与结核病的耐药性有关，结核病是一种传染性呼吸道疾病，由于耐多药而越来越难以治疗。以前的工作已经证实，维生素 D 可诱导巨噬细胞对结核分枝杆菌产生抗菌功能。在本文中，我们通过整合转录组和机制研究，报道了维生素 D 在结核病中的一个新的代谢作用。转录组分析显示，人类结核病和感染的巨噬细胞中维生素 D 受体（VDR）与脂质代谢之间存在关联。维生素 D 处理感染的巨噬细胞可消除感染诱导的脂滴积累，这是结核分枝杆菌在细胞内生长所必需的。其他转录组学结果表明，维生素 D 下调了感染巨噬细胞中促脂肪生成的过氧化物酶体增殖物激活受体 γ（PPARγ）。PPARγ 激动剂逆转了 VDR 的抗脂肪生成和抗菌作用，表明 VDR 与 PPARγ 信号通路在调节维生素 D 功能方面存在联系。这些发现表明，针对脂质代谢的基于宿主的辅助抗结核治疗具有潜力。
