Vitamin D has long been linked to resistance to tuberculosis, an
infectious respiratory disease that is increasingly hard to treat due to
multidrug resistance. Previous work established that vitamin D induces
macrophage antimicrobial functions against Mycobacterium
tuberculosis. Here 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 pro-adipogenic
peroxisome proliferator-activated receptor gamma (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 potential for host-based, adjunct antituberculosis therapy targeting
lipid metabolism.