Effect of 1,25-dihydroxyvitamin D3 on the expression of mannose receptor, DC-SIGN and autophagy genes in pulmonary tuberculosis

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 99; pp. 1 - 10
• Main Authors: Afsal, K, Selvaraj, P
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-07-2016
• Subjects: Adult; Antimicrobial Cationic Peptides; Autophagy; Autophagy - drug effects; Autophagy - genetics; Autophagy-Related Protein 5 - genetics; Autophagy-Related Protein 5 - metabolism; Beclin-1 - genetics; Beclin-1 - metabolism; Calcitriol - pharmacology; Case-Control Studies; Cathelicidins - metabolism; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cells, Cultured; Female; Gene Expression Regulation - drug effects; Humans; Immunologic Factors - pharmacology; Infectious Disease; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Macrophages - microbiology; Male; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Middle Aged; Monocyte/macrophage; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Monocytes - microbiology; Mycobacterium tuberculosis - immunology; Phagocytosis; Phagocytosis - drug effects; Pulmonary/Respiratory; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Time Factors; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - metabolism; Tuberculosis, Pulmonary - microbiology; Vitamin D; Monocyte/macrophage; Tuberculosis; Vitamin D; Autophagy; Phagocytosis
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2016.03.010

Summary 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ] is a powerful immuno-modulator, which enhances expression of antimicrobial peptides and induces autophagy in monocytes/macrophages. Since 1,25(OH)2 D3 increases the phagocytic potential of monocytes/macrophages, we have explored the effect of 1,25(OH)2 D3 on the expression of receptors such as mannose receptor (CD206) and DC-SIGN (CD209) as well as autophagy genes such as ATG5 and Beclin-1 (BECN1) in monocytes/macrophages of healthy controls (HCs) and pulmonary tuberculosis (PTB) patients with and without cavitary disease. Peripheral blood mononuclear cells (PBMCs) were isolated from 40 HCs and 40 PTB patients and were cultured for 72 h with Mtb in the presence or absence of 1,25(OH)2 D3 at 10−7  M concentration. 1,25(OH)2 D3 significantly upregulated the expression of mannose receptor , ATG5 and BECN1 ; whereas DC-SIGN expression was suppressed in Mtb infected cells of both study groups (p < 0.05). The 1,25(OH)2 D3 -induced expression of CD206 , ATG5 and BECN1 genes was lower in PTB patients compared to HCs, whereas expression of these genes was impaired in PTB patients with cavitary disease. Moreover, the relative expression of ATG5 and BECN1 was positively correlated with monocyte/macrophage phagocytosis and cathelicidin antimicrobial peptide gene expression in HCs and PTB patients (p < 0.05). Our study results suggest that vitamin D supplementation in PTB patients without cavitary disease could enhance innate immune functions and may help to control intracellular growth of mycobacteria in macrophages.