Vitamin D and Macrophage Functions in Tuberculosis

Abstract

Mononuclear phagocytes like monocytes/macrophages engulf microbes and mediate intracellular killing through different mechanisms such as production of anti-microbial peptides, reactive oxygen/nitrogen intermediates and autophagy induction. However, intracellular pathogens like M. tuberculosis evades from macrophage defense mechanisms by various strategies to adapt the intracellular environment of macrophages and creating a major host cell niche for its growth and survival. 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] is the active form of vitamin D, which is shown to be involved in immuno-modulation in various immune cells including macrophages. Genomic actions of 1,25(OH) 2 D 3 exert through vitamin D receptor, which is expressed constitutively in macrophages. Various studies revealed that 1,25(OH) 2 D 3 enhances the macrophage phacocytosis by upregulating the surface receptors including CD14 and mannose receptor. Moreover, 1,25(OH) 2 D 3 enhances the antimicrobial effects of macrophages by upregulating the expression of antimicrobial peptides such as cathelicidin and defensin, which inhibit the intracellular growth of M. tuberculosis . 1,25(OH) 2 D 3 mediated cathelicidin expression upregulates the autophagy genes and enhance the fusion of phagosome containing M. tuberculosis with lysosome. Apart from antimicrobial effects, 1,25(OH) 2 D 3 also modulates the antigen presentation and secretion of chemokines, cytokines and other factors of macrophages. In conclusion, it has been suggested that 1,25(OH) 2 D 3 enhances macrophage innate immune functions by upregulating the antimicrobial efficiency, which could be beneficial to the host during active tuberculosis disease. This suggests that vitamin D supplementation may be useful as an adjunct during anti-TB treatment in tuberculosis.