Efeitos contrastantes da vitamina D sobre a resposta imune inata e adquirida e seu impacto na recuperação da tuberculose
DOI:
https://doi.org/10.34019/1982-8047.2018.v44.22232Palabras clave:
Vitamina D, 25(OH)D, Sistema imune, Tuberculose, TratamentoResumen
A vitamina D é um hormônio essencial para o organismo, podendo ser obtida da dieta ou, principalmente, gerada pela pele após exposição à luz solar ultravioleta B. Na sua forma ativa (1,25(OH)2D) ela controla a absorção de cálcio e fósforo do intestino para a corrente sanguínea e participa de diversos processos celulares e fisiológicos. A ligação da 1,25(OH)2D ao receptor da vitamina D (VDR) presente em diversas células, como as células do sistema imunológico, induz a transcrição de genes que podem, por exemplo, modular a resposta imune inata e adquirida. A deficiência de vitamina D ou do VDR é associada a problemas de saúde como desordens esqueléticas, hipertensão, doenças cardiovasculares, diabetes mellitus, dislipidemias, doenças autoimunes e doenças infecciosas. Neste sentido, a suplementação com vitamina D tem sido proposta como uma possível medida preventiva, podendo ser aplicada em muitas patologias, em especial na tuberculose. Principal causa de morte por um único agente infeccioso, a tuberculose é responsável por cerca de 1,3 milhões de óbitos por ano no mundo. Publicações recentes apontam efeitos diversos da vitamina D na resposta imune inata e adquirida. A 1,25(OH)2D3 na presença do interferon (IFN)-γ é capaz de aumentar a atividade bactericida do macrófago contra o M. tuberculosis, aumentando a produção de peptídios antimicrobianos e estimulando a autofagia, favorecendo assim a lise de bacilos localizados em fagossomos. Por outro lado, a vitamina D em linfócitos T mostra efeito tolerogênico que favorece o controle de respostas inflamatórias excessivas. Neste trabalho de revisão são apresentados estudos recentes envolvendo efeitos da vitamina D na resposta imune inata e adquirida. Além disso, considerações sobre deficiência de vitamina D e maior risco de contrair tuberculose, e efeitos contrastantes da suplementação com vitamina D na prevenção e tratamento da TB, são discutidos.
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AGARWAL, A.; GUPTA, S. K.; SUKUMAR, R. Hyperparathyroidism and malnutrition with severe vitamin D deficiency. World Journal of Surgery, v. 33, n. 11, p. 2303-2313, nov. 2009.
AKIRA, S.; TAKEDA, K. Toll-like receptor signalling. Nature Reviews Immunology, v. 4, n. 7, p. 499-511, jul. 2004.
BACCHETTA, J. et al. Suppression of iron-regulatory hepcidin by vitamin D. Journal of American Society of Nephrology, v. 25, n. 3, p. 564‒572, mar. 2014.
BELDERBOS, M. E. et al. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics, v. 127, n. 6, p. 1513-1520, feb. 2011.
BENDIK, I. et al. Vitamin D: A critical and essential micronutrient for human health. Frontiers in Physiology, v. 5, n. 248, p. 1-14, jul. 2014.
BERGMAN, P. et al. Vitamin D supplementation improves well-being in patients with frequent respiratory tract infections: a post hoc analysis of a randomized, placebo-controlled trial. BMC Research Notes, v. 8, p. 498-502, sep. 2015.
BITETTO, D. Complementary role of vitamin D deficiency and the interleukin‐28B rs12979860 C/T polymorphism in predicting antiviral response in chronic hepatitis C. Hepatology, v. 53, n. 4, p. 1118-1126, jan. 2011.
CAMPBELL, G. R.; SPECTOR, S. A. Hormonally active vitamin D3 (1α,25-dihydroxycholecalciferol) triggers autophagy in human macrophages that inhibits HIV-1 infection. The Journal of Biological Chemistry, v. 286, n. 21, p. 18890–18902, may. 2011.
CAO, Y. et al. Vitamin D receptor gene fokI polymorphisms and tuberculosis susceptibility: a meta-analysis. Archives of Medical Science, v. 12, n. 5, p. 1118–1134, may. 2016.
CETINKAYA, M. et al. Lower Vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. Journal of Perinatology, v. 35, n. 1, p. 39-45, jan. 2015.
CHEN, Y. et al. Vitamin D receptor inhibits NF-κB activation by interacting with IKKβ protein. The Journal of Biological Chemistry, v. 288, n. 27, p. 19450–19458, jul. 2013.
CHERAYIL, B. J. The role of iron in the immune response to bacterial infection. Immunology Research, v. 50, n. 1, p. 1‒9, may. 2011.
CHUN, R. F.; ADAMS, J. S.; HEWISON, M. Immunomodulation by vitamin D: implications for TB. Expert Review of Clinical Pharmacology, v. 4, n. 5, p. 583-591, set. 2011.
CHUN, R. F. et al. Vitamin D-binding protein directs monocyte responses to 25-hydroxy- and 1,25-dihydroxyVitamin D. The Journal of Clinical Endocrinology and Metabolism, v. 95, n. 7, p. 3368‒3376, jul. 2010.
CLEMENS, T. L. et al. Increased skin pigment reduces the capacity of skin to synthesis vitamin D3. Lancet, v. 1, n. 8263, p. 74‒76, jan. 1982.
COELHO, L. et al. Vitamin D3 supplementation in HIV infection: effectiveness and associations with antiretroviral therapy. Nutrition Journal, v. 14, p. 81-89, ago. 2015.
COUSSENS, A. K. et al. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proceedings of the National Academy of Sciences USA, v. 109, n. 38, p. 15449–15454, 2012.
DALEY, P. et al. Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. The Lancet Infectious Diseases, v. 15, n. 5, p. 528-534, may. 2015.
DERETIC, V.; SAITOH, T.; AKIRA, S. Autophagy in infection, inflammation and immunity. Nature Reviews Immunology, v. 13, n. 10, p. 722‒737, oct. 2013.
DERETIC, V.; LEVINE, B. Autophagy, immunity, and microbial adaptations. Cell Host & Microbe, v. 5, n. 6, p. 527-549, jun. 2009.
DI ROSA, M. et al. Vitamin D3: a helpful immuno-modulator. Immunology, v. 134, n. 2, p. 123-139, oct. 2011.
ESPOSITO, S.; LELII, M. Vitamin D and respiratory tract infections in childhood. BMC Infectious Diseases, v. 15, p. 487-496, oct. 2015.
FABRI, M. et al. Role of autophagy in the host response to microbial infection and potential for therapy. Current Opinion in Immunology, v. 23, n. 1, p. 65‒70, feb. 2011a.
FABRI, M. et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Science Translational Medicine, v. 3, n. 104, p. 104ra102, oct. 2011b.
GANMAA, D. et al. Vitamin D, tuberculin skin test conversion, and latent tuberculosis in Mongolian school-age-children: a randomized, double-blind, placebo-controlled feasibility trial. The American Journal of Clinical Nutrition, v. 96, n. 2, p. 391-396, aug. 2012.
GIBNEY, K. B. et al. Vitamin D deficiency is associated with tuberculosis and latent tuberculosis infection in immigrants from sub-Saharan Africa. Clinical Infectious Diseases, v. 46, n. 3, p. 443-446, feb. 2008.
GINDE, A. A.; MANSBACH, J. M.; CAMARGO, C. A. Jr. Association between serum 25-hydroxyVitamin D and upper respiratory tract infection in the third national health and nutrition examination survey. Archives Internal Medicine, v. 169, n. 4, p. 384–390, feb. 2009.
GOMBART, A. F.; BORREGAARD, N.; KOEFFLER, H. P. Human cathelicidin antimicrobial peptide (camp) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyVitamin D3. Faseb Journal, v. 19, n. 9, p. 1067-1077, jul. 2005.
GONÇALVES-MENDES, N. et al. Impact of vitamin D supplementation on influenza vaccine response and immune functions in deficient elderly persons: a randomized placebo-controlled trial. Frontiers in immunology, v. 10, n. 65, feb. 2019.
GREEN, M. Cod liver oil and tuberculosis. British Medical Journal, v. 343, p. 7505-7510, dec. 2011.
HEWISON, M. Antibacterial effects of Vitamin D. Nature Reviews Endocrinology, v. 7, n. 6, p. 337-345, jan. 2011.
HOLICK, M. F. et al. Photometabolism of 7-dehydrocholesterol to preVitamin D3 in skin. Biochemical Biophysical Research Communication, v. 76, n. 1, p. 107-114, may. 1977.
HU, Q. et al. Vitamin D receptor gene associations with pulmonary tuberculosis in a tibetan chinese population. BMC Infectious Diseases, v. 16, p. 469- 475, sep. 2016.
JEFFERY, L. E. et al. Availability of 25-hydroxyVitamin D(3) to APCs controls the balance between regulatory and inflammatory T cell responses. Journal of Immunology, v. 189, n. 11, p. 5155-5164, dec. 2012.
JEFFERY, L.E. et al. 1,25-dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. Journal of Immunology. v. 183, n. 9, p. 5458‒5467, nov. 2009.
KEARNS, M. D. et al. Impact of vitamin D on infectious disease. The American Journal of the Medical Sciences, v. 349, n. 3, p. 245-262, mar. 2015.
KLUG-MICU, G. M. et al. CD40 ligand and interferon- induce an antimicrobial response against Mycobacterium tuberculosis in human monocytes. Immunology, v. 139, n.1, p. 121-128, may. 2013.
KOTA, S. K. et al. Effect of vitamin D supplementation in type 2 diabetes patients with pulmonary tuberculosis. Diabetes & Metabolic Syndrome, v.5, n. 2, p.85–89, 2011.
KRONER, J. C.; SOMMER, A.; FABRI, M. Vitamin D every day to keep the infection away? Nutrients, v. 7, n. 6, p. 4171 - 4188, may. 2015.
LANG, P. O. et al. How important is vitamin D in preventing infections? Osteoporosis International, v. 24, n. 5, p. 1537–1553, may. 2013.
LARCOMBE, L. et al. Effect of vitamin D supplementation on mycobacterium tuberculosis-induced innate immune responses in a canadian dene first nation’s cohort. PLoS ONE, v. 7, n. 7, p. E40692, 2012.
LEBLANC, E. S. et al. Associations between 25-hydroxyvitamin D and weight gain in elderly women. Journal of Women’s Health, v. 21, n. 10, p. 1066-1073, oct. 2012.
LIN, Y. et al. Vitamin D is required for ILC3 derived IL-22 and protection from citrobacter rodentium infection. Frontiers in Immunology, jan. 2019.
LIU, P. T. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, v. 311, n. 5768, p. 1770-1773, Mar. 2006.
LIU, P. T. et al. Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses. PLoS ONE, v. 4, n. 6, p. 5810-5822, jun. 2009.
LIU, P. T. et al. MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nature Medicine, v. 18, n. 2, p. 267-273, jan. 2012.
MACLAUGHLIN, J.; HOLICK, M. F. Aging decreases the capacity of human skin to produce vitamin D3. The Journal of Clinical Investigation, v. 76, n. 4, p. 1536‒1538, oct. 1985.
MAGHZI, H. et al. Association between acute infectious mononucleosis and vitamin D deficiency. Viral Immunology, v. 29, n.7, p. 398-400, sep. 2016.
MARTINEAU, A. R. et al. A single dose of vitamin D enhances immunity to mycobacteria. American Journal of Respiratory and Critical Care Medicine, v. 176, n.2, p. 208-213, jul. 2007.
MARTINEAU, A. R. et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet, v. 377, n. 9761, p. 242-250, jan. 2011.
MILOVANOVIC, M. et al. Vitamin D deficiency is associated with increased IL-17 and TNF levels in patients with chronic heart failure. Arquivos Brasileiros de Cardiologia, v. 98, n. 3, p. 259-265, mar. 2012.
MILY, A. et al. Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis. BioMed Central Pulmonary Medicine, v. 13, p. 23-30, apr. 2013.
MORCOS M. M. et al. Vitamin D administration to tuberculous children and its value. Bollettino Chimico Farmaceutico, v. 137, n. 5, p. 157-164, 1998.
NNOAHAM, K. E.; CLARKE, A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. International Journal of Epidemiology, v.37, n. 1, p.113-119, feb. 2008.
NURSYAM, E. W.; AMIN, Z.; RUMENDE, C. M. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Medica Indonesiana, v. 38. n. 1, p. 3-5, 2006.
OJAIMI, S. et al. Vitamin D deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study. Journal of Translational Medicine, v. 11, n. 1, p. 176-182, jul. 2013.
PAREEK, M. et al. Vitamin D deficiency and TB disease phenotype. Thorax, v. 70, n. 12, p. 1171-1180, dec. 2015.
PAPAPOULOS, S. E. et al. 1,25-dihydroxycholecalciferol in the pathogenesis of the hypercalcemia of sarcoidosis. Lancet, v. 1, n. 8117, p. 627-630, mar. 1979.
PENNA, G.; ADORINI, L. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. Journal of Immunology, v. 164, n. 5, p. 2405‒2411, mar. 2000.
PLUDOWSKI, P. et al. Vitamin D supplementation guidelines. The Journal of Steroid Biochemistry and Molecular Biology, v. 175, p. 125-135, jan. 2018.
RALPH, A. P. et al. L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial. PLoS ONE, v. 8, n. 8, e70032, 2013.
RAMANATHAN, B. et al. Cathelicidins: microbicidal activity, mechanisms of action, and roles in innate immunity. Microbes and Infection, v. 4, n. 3, p. 361–372, mar. 2002.
RIGBY, W. F.; DENOME, S.; FANGER, M. W. Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyVitamin D3. Specific inhibition at the level of messenger RNA. The Journal of Clinical Investigation, v. 79, n. 6, p. 1659‒1664, jun. 1987.
RIVAS-SANTIAGO, B. et al. Ability of innate defence regulator peptides IDR-1002, IDR-hh2 and IDR-1018 to protect against Mycobacterium tuberculosis infections in animal models. PLoS ONE, v. 8, n. 3, e59119, 2013.
ROOK, G. A. et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology, v. 57, n. 1, p. 159-163, jan. 1986.
SALAHUDDIN, N. et al. Vitamin D accelerates clinical recovery from tuberculosis: results of the succinct study [supplementary cholecalciferol in recovery from tuberculosis]. A randomized, placebo-controlled, clinical trial of vitamin D supplementation in patients with pulmonary tuberculosis'. BMC Infectious Diseases, v. 13, n. 22, 2013.
SCHUCH, N. J.; GARCIA, V. C.; MARTINI, L. A. Vitamina D e doenças endocrinometabólicas. Arquivos Brasileiros de Endocrinologia & Metabologia, v. 53, n. 5, p. 625-633, jul. 2009.
SINGH, I. et al. VDR polymorphism, gene expression and vitamin D levels in leprosy patients from North Indian population. PLoS Neglected Tropical Diseases, v. 12, n. 11, nov. 2018.
TALAT, N. et al. Vitamin D deficiency and tuberculosis progression. Emerging infectious diseases, v. 16, n. 5, p. 853-855, may. 2010.
TANG, J. et al. Calcitriol suppresses antiretinal autoimmunity through inhibitory effects on the Th17 effector response. Journal of Immunology, v. 182, n. 8, p. 4624‒4632, apr. 2009.
TEKIN, M. et al. The association between vitamin D levels and urinary tract infection in children. Hormone Research in Paediatrics, v. 83, n. 3, p. 198-203, jan. 2015.
UNGER, W. W. et al. Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1. European Journal of Immunology, v. 39, n. 11, p. 3147‒3159, nov. 2009.
VANLINT, S. Vitamin D and obesity. Nutrients, v. 5, n. 3, p. 949-956, mar. 2013.
VELDMAN, C. M.; CANTORNA, M. T.; DELUCA, H. F.; Expression of 1,25-dihydroxy Vitamin D(3) receptor in the immune system. Archives of Biochemistry and Biophysics, v. 374, n. 2, p. 334–338, feb. 2000.
VERWAY, M. et al. Vitamin D induces interleukin-1 expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection. PLoS Pathogens, v. 9, n. 6, p. e1003407 Jun. 2013.
VIEIRA, O. V.; BOTELHO, R. J.; GRINSTEIN, S. Phagosome maturation: aging gracefully. The Biochemical Journal, v. 366, p. 689-704, sep. 2002.
VON ESSEN, M.R. et al. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nature Immunology, v. 11, n. 4, p. 344‒349, apr. 2010.
WEJSE, C. et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. American Journal of Respiratory and Critical Care Medicine, v. 179, n. 9, p. 843-850, 2009.
WHO. World Health Organization. Global tuberculosis report 2018, Geneva, Sep, 2018. Disponível em: https://www.who.int/tb/publications/global_report/en/ . Acesso em 2 Jan. 2019.
WU, S. et al. Vitamin D receptor negatively regulates bacterial-stimulated NFkappaB activity in intestine. The American Journal of Pathology, v. 177, n. 2, p.686–697, ago. 2010.
WU, S.; SUN, J. Vitamin D, vitamin D receptor, and macroautophagy in inflammation and infection. Discovery Medicine, v. 11, n. 59, p. 325-335, apr. 2011.
YANG, C. S. et al. NADPH oxidase 2 interaction with TLR2 is required for efficient innate immune responses to mycobacteria via cathelicidin expression. Journal of Immunology, v. 182, n. 6, p. 3696-3705, mar. 2009.
YUZEFPOLSKI, Y. et al. Vitamin D receptor signals regulate effector and memory CD8 T cell responses to infections in mice. The Journal of Nutrition, v. 144, n. 12, p. 2073-2082, dec. 2014.
ZHANG, R.; NAUGHTON, D. P. Vitamin D in health and disease: current perspectives. Nutrition Journal, v. 9, p. 65-77, dec. 2010.
ZHANG, Y. et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. Journal of Immunology, v. 188, n. 5, p. 2127‒2135, mar. 2012.
ZITTERMANN, A. et al. Vitamin D and airway infections: a european perspective. European Journal of Medical Research, v. 21, p. 14-23, mar. 2016.
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