The role of vitamin D deficiency in antituberculous protection


BACKGROUND. The main task of modern phthysiology is a comprehensive search for ways to optimize the etiotropic and the pathogenetic treatment of tuberculosis (TB). The search for improved treatment in addition to etiotropic antimicrobial therapy lies in the plane of improving pathogenetic therapy. Analysis of the available scientific sources suggests that the efficacy of TB treatment can be improved by adding vitamin D to the pathogenetic treatment, as vitamin D metabolites support the innate immune response to Mycobacterium tuberculosis.

OBJECTIVE. To determine the role of vitamin D in the immunopathogenesis of the inflammatory response in pulmonary TB and to assess the prospects of its impact on improving the effectiveness of treatment by analyzing information from available scientific sources on this topic.

MATERIALS AND METHODS. The study was performed for the period December 2020 – August 2021. The search was conducted by


pulmonary tuberculosis, vitamin D, mechanism of action, pathogenesis, treatment. Access to various full-text and abstract databases was used as the main source of research.

RESULTS AND DISCUSSION. A large number of studies conducted so far prove the link between vitamin D deficiency and the occurrence of pulmonary TB. Vitamin D receptors have been found to be present on various surfaces of immune cells, including T and B cells, indicating that they need vitamin D to perform cellular functions. Vitamin D has been shown to increase the phagocytic activity of macrophages, and that monocytes incubated with cholecalciferol (vitamin D3) metabolites induce anti-TB activity. A number of studies have shown that vitamin D increases the body’s production of the antimicrobial/antimycobacterial peptide LL-37, a member of the cathelicidin petelide family. Therefore, the narrowly analyzed analysis according to the literature suggests that in the conditions of full vitamin D status of the human body the course of TB will be favorable, and in case of vitamin D deficiency – which is primarily associated with genetic polymorphisms, the course of TB may be unfavorable.

CONCLUSIONS. Vitamin D functionates as one of the activators of macrophages and plays a role in the immune defense of the human body against mycobacterial TB. The inclusion of vitamin D in the program of complex treatment of TB infection is promising, as it enhances the production of antimicrobial/antimycobacterial peptide LL-37. It can be used as one of the components of TB prevention in children.

Keywords: vitamin D, tuberculosis, pathogenesis, inflammation, treatment.


Marchenko A.F., Petrenko V.I., Golubovska O.A. ta in. Porushennia funktsii pechinky u khvorykh na vpershe diahnostovanyi tuberkuloz lehen zalezhno vid naiavnosti suputnikh virusnykh hepatytiv [Dysfunction of the liver in patients with newly diagnosed pulmonary tuberculosis, depending on the presence of concomitant viral hepatitis]. Tuberculosis. Lung diseases. HIV infection. 2018; 1: 15-20.

Pavlova Ye.S. Effektivnost lecheniia vpervyie vyiavlennykh bolnykh destruktivnym tuberkulezom legkikh s patologiiei zheludochno-kishechnogo trakta: avtoref. dis. kand. med. nauk 14.00.26. – Moscow, 2005. – 115 p.

Todoriko L.D., Petrenko V.I., Hryshyn M.M. Rezystentnist mikobakterii tuberkulozu: mify ta realnist [Resistance of Mycobacterium tuberculosis: myths and reality]. Tuberculosis. Lung diseases. HIV infection. 2014; 1: 60-67.

Cherenko S.O. Tuberkuloz i khronichne obstruktyvne zakhvoriuvannia lehen – spilni mekhanizmy patohenezu ta vplyv vitaminu D na yikh perebih [Tuberculosis and chronic obstructive pulmonary disease – common mechanisms of pathogenesis and effect of vitamin D on their course]. Ukr. Chemotherapy J. 2012; 1-2: 91-97.

Adams J.S., Ren S., Liu P.T., et al. Vitamin D directed rheostatic regulation of monocyte antibacterial responses. J. Immunol. 2009; 182: 4289-4295.

Aranow C. Vitamin D and the immune system. J. Investig. Med. 2011; 59 (6): 881-886.

Bae M., Kim H. Mini-review on the roles of vitamin C, vitamin D, and selenium in the immune system against COVID-19. Molecules. 2020 Nov 16; 25 (22): 5346.

Bals R., Wilson J.M. Cathelicidins − a family of multifunctional antimicrobical peptides. Cell Mol. Life Sci. 2003; 60: 711-720.

Boonstra A., Barrat F.J., Crain C., et al. 1alpha,25-dihydroxyvitamin D3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol. 2001; 167 (4): 4974-4980.

Cantorna M.T. Why do T cells express the vitamin D receptor? Ann. NY Acad. Sci. 2011; 1217: 77-82.

Chan T.Y. Vitamin D deficiency and susceptibility to tuberculosis. Calcif. Tissue Int. 2000; 66 (6): 476-478.

Cheng J.B., et al. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc. Natl. Acad. Sci. USA. 2004; 101: 7711-7715.

Chocano-Bedoya P., Ronnenberg A.G. Vitamin D and tuberculosis. Nutr. Res. 2009; 67 (5): 289-293.

Crowle A.J., Ross E.J. Comparative abilities of various metabolites of vitamin D to protect cultured human macrophages against tubercle bacilli. J. Leukoc. Biol. 1990; 47: 545-550.

Ding A., et al. Macrophage deactivating factor and transforming growth factor beta 1, 2 and 3 inhibit induction of macrophage nitrogen oxide synthesis by IFN-gamma. J. Immunol. 1990; 145: 990-995.

Eun-Kyeong J. Innate immunity to mycobacteria: vitamin D and autophagy. Cell. Microb. 2010; 128 (8): 1026-1035.

Gibney K.B., MacGregor L., Leder K., et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clin. Infect. Dis. 2008; 46 (3): 443-446.

Hansdottir S. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J. Immunol. 2008; 181: 7090-7099.

Hmama Z., Sendide K., Talal A., et al. Quantitative analysis of phagolysosome fusion in intact cells: inhibition by mycobacterial lipoarabinomannan and rescue by an 1alpha, 25-dihydroxyvitamin D3-phosphoinositide 3-kinase pathway. J. Cell Sci. 2004; 117 (Pt. 10): 2131-2140.

Jacobs M., et al. Tumor necrosis factor is critical to control tuberculosis infection. Microbes Infect. 2007; 9 (5): 623-628.

Kaufmann S.H. Protection against tuberculosis: cytokines, T cells, and macrophages. Ann. Rheum. Dis. 2002; 61 (2): 54-58.

Kawada N., Sakaki T., Ohta M., Inouye K. Metabolism of vitamin D(3) by human CYP27A1. Biochem. Biophys. Res. Commun. 2000; 273: 977-984.

Kearns M.D., Tangpricha V. The role of vitamin D in tuberculosis. J. Clin. Transl. Endocrinol. 2014; 1 (4): 167-169.

Lin P.L., Flynn J.L. Understanding latent tubercolosis: a moving target. J. Immunol. 2010; 185 (1): 15-22.

Liu P.T., Stenger S., Li H., Wenzel I., et al. Toll-like receptors triggering of a vitamin D mediated anti-microbical response. Science. 2006; 311: 1770-1773.

Liu P.T., Stenger S., Tang D.H., Modlin R.L. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol. 2007; 179 (4): 2060-2063.

Meintjes G., Wilkinson K.A., Rangaka M.X., et al. Type 1 helper T cells and FoxP3-positive T cells in HIV-tuberculosis-associated immune reconstitution inflammatory syndrome. Am. J. Respir. Crit. Care Med. 2008; 178 (10): 1083-1089.

Negri A.L. Proximal tubule endocytic apparatus as the specific renal uptake mechanism for vitamin D-binding protein/25(OH)D3 complex. Nephrology (Carlton). 2006; 11: 510-515.

Nnoaham K.E., Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int. J. Epidemiol. 2008; 37 (1): 113-119.

Overbergh L., Cecallome B., Waer M., et al. 1alpha, 25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1 / T-helper 2 immune shift in NOD mice immunized with GAD65 (p. 524-543). Diabetes. 2000; 49 (8): 1301-1307.

Penna G.L. 1alpha, 25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 2000; 164: 2405-2411.

Periyasamy K.M., Ranganathan U.D., Tripathy S.P., Bethunaickan R. Vitamin D – a host directed autophagy mediated therapy for tuberculosis. Mol. Immunol. 2020 Nov; 127: 238-244.

Rivas-Santiago B., Hernandez-Pando R., Carranza C., et al. Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infect. Immun. 2008 Mar; 76 (3): 935-941.

Rook G.A., Steele J., Fraher L., et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology. 1986; 57 (1): 159-163.

Sasidharan P.K., Rajeev E., Vijayakumari V. Tuberculosis and vitamin D deficiency. J. Assoc. Physicians India. 2002; 50: 554-558.

Spellberg B., Edwards J. Type 1 / type 2 immunity in infectious diseases. Clin. Infect. Diseases. 2001; 32 (1): 76-102.

St-Arnaud R. The direct role of vitamin D on bone homeostasis. Arch. Biochem. Biophys. 2008; 473: 225-230.

Tadokera R., Meintjes G., Skolimowska K.H., et al. Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome. Eur. Respir. J. 2011; 37 (5): 1248-1259.

Tadokera R., Meintjes G.A., Wilkinson K.A., et al. Matrix metalloproteinases and tissue damage in HIV‐tuberculosis immune reconstitution inflammatory syndrome. Eur. J. Immunol. 2014; 44 (1): 127-136.

Ustianowski A., Shaffer R., Collin S., et al. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J. Infect. 2005; 50 (5): 432-437.

Vidyarani M., Selvaraj P., Prabhu A. Interferon gamma (IFN-gamma) & interleukin-4 (I-4) gene variants & cytokine levels in pulmonary tuberculosis. Ind. J. Med. Res. 2006; 124 (4): 403-410.

Wejse C., Olesen R., Rabna P., et al. Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls. Am. J. Clin. Nutr. 2007; 86 (5): 1376-1383.

Williams B., Williams A.J., Anderson S.T. Vitamin D deficiency and insufficiency in children with tuberculosis. Pediatr. Infect. Dis. J. 2008; 27 (10): 941-942.

Yuk J.M., Shin D.M., Lee H.M., et al. Vitamin D induces autophagy in human monocytes/macrophages via cathelcidin. Cell Host Microbe. 2009; 6 (3): 231-243.

How to Cite
Todoriko, L., Toderika, Y., Shevchenko, O., Pidverbetska, O., & Pidverbetskyi, O. (2021). The role of vitamin D deficiency in antituberculous protection. Infusion & Chemotherapy, (4), 38-44.

Author Biographies

L.D. Todoriko, Bukovinian State Medical University, Chernivtsi, Ukraine

Todoriko Lilіa Dmytrivna
Нead of Department of Phthisiology and Pulmonology
DM, professor.
2, Theatralna sq., Chernivtsi, 58002, Ukraine.
Тел./факс: +38 (0372) 55-37-54.

Ya.I. Toderika, Bukovinian State Medical University, Chernivtsi, Ukraine

Toderika Yana Ivanivna
Intern, senior Laboratory Assistant of the Department of Tuberculosis and Pulmonology
2, Theatralna sq., Chernivtsi, 58002, Ukraine.

O.S. Shevchenko, Kharkiv National Medical University, Kharkiv, Ukraine

Shevchenko Olga Stanislavivna
Head of the Department of Phthisiology and Pulmonology
MD, professor.
4, Avenue of Science, Kharkiv, 61022, Ukraine.

O.V. Pidverbetska, Bukovinian State Medical University, Chernivtsi, Ukraine

Pidverbetska Olena Valeriivna
Associate Professor of the Department of Phthisiology and Pulmonology
2, Theatralna sq., Chernivtsi, 58002, Ukraine.

O.Ya. Pidverbetskyi, Bukovinian State Medical University, Chernivtsi, Ukraine

Pidverbetskyi Oleh Yaroslavovych
Аssistant of Department of Phthisiology & Pulmonology
2, Theatralna sq., Chernivtsi, 58002, Ukraine.

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