title: Effect of 1,25-dihydroxyvitamin D3 on the expression of mannose receptor, DC-SIGN and autophagy genes in pulmonary tuberculosis.
abstract: 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a powerful immuno-modulator, which enhances expression of antimicrobial peptides and induces autophagy in monocytes/macrophages. Since 1,25(OH)2D3 increases the phagocytic potential of monocytes/macrophages, we have explored the effect of 1,25(OH)2D3 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)2D3 at 10(-7) M concentration. 1,25(OH)2D3 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)2D3-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.
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, 1, Mayor Sathyamoorthy Road, Chennai 600 031, India.
authors.forename: K
authors.initials: K
authors.lastname: Afsal
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (Formerly Tuberculosis Research Centre), Indian Council of Medical Research, 1, Mayor Sathyamoorthy Road, Chennai 600 031, India. Electronic address: p.selvaraj53@yahoo.com.
authors.forename: P
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D016022:Case-Control Studies; D054804:Cathelicidins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D023181:Antimicrobial Cationic Peptides; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D002117:Calcitriol; D054804:Cathelicidins; D015815:Cell Adhesion Molecules; D007155:Immunologic Factors; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C502778:ATG5 protein, human; C491997:BECN1 protein, human
keywords: Autophagy; Monocyte/macrophage; Phagocytosis; Tuberculosis; Vitamin D