Influence of Cdx2 and TaqI Gene Variants on Vitamin D3 Modulated Intracellular Chemokine Positive T-Cell Subsets in Pulmonary Tuberculosis.

PURPOSE: We studied the effect of 1,25(OH)2D3 (vitamin D3) on intracellular chemokine-positive T-cell subsets in whole blood cultures of healthy controls and patients with pulmonary tuberculosis. METHODS: Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. The regulatory role of the Cdx2 and 3'UTR TaqI gene variants on chemokine-positive T-cell subsets was studied from culture filtrate antigen stimulated with or without vitamin D3 treated whole blood cultures of 60 healthy controls and 50 patients with pulmonary tuberculosis. FINDINGS: Vitamin D3 significantly suppressed monocyte chemoattractant protein 1, macrophage inhibitory protein (MIP)-1α, MIP-1ß, regulated on activation, normal T-cell expressed and secreted (RANTES), and interferon-γ inducible protein 10 (IP-10)-positive T-cell subsets compared with culture filtrate antigen stimulated cells without vitamin D3 treatment. In the Cdx2 AA genotype, vitamin D3 decreased MIP-1α, MIP-1ß, and RANTES-positive T cells compared with the GG genotype. Whereas in the TaqI tt genotype, decreased MIP-1ß and RANTES and increased IP-10-positive T cells were observed compared with the TT genotype in vitamin D3 treated cells (p < 0.05). IMPLICATIONS: This study suggests that vitamin D3 may regulate the chemokine-positive T cells through the Cdx2 AA and TaqI tt genotypes. This could be helpful to regulate chemokine-mediated inflammatory response during active disease condition. Hence, vitamin D3 supplementation along with tuberculosis drugs may be useful for faster recovery from the disease.

Vitamin D: Immuno-modulation and tuberculosis treatment.

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.