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J Immunol. 2014 Jul 1;193(1):30-34. doi: 10.4049/jimmunol.1400736. Epub 2014 Jun 4.

Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis infection.

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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.
Contributed equally


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.

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