Skip to main content

Vitamin D and the Innate Immune Response

  • 1087 Accesses

Part of the Respiratory Medicine book series (RM,volume 3)

Abstract

Active vitamin D metabolites play a major role in key functions of the innate immune response. Triggering of the vitamin D receptor (VDR) by those metabolites has been demonstrated to mediate the expression of antimicrobial peptides, induction of autophagy, as well as the production of reactive oxygen species and reactive nitrogen species as mechanisms of host defense. The role of vitamin D has been well characterized in the context of tuberculosis from both a molecular and epidemiological standpoint. Activation of Toll-like receptors, a family of innate immune pattern recognition receptors, on human macrophages with Mycobacterium tuberculosis-derived ligands results in activation of the vitamin D pathway, including (1) the conversion of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)2D), (2) activation of the VDR, and (3) antimicrobial activity against intracellular M. tuberculosis infection. This provides a potential explanation for the association between the host vitamin D status with susceptibility to tuberculosis infection and disease.

Keywords

  • Innate immunity
  • Toll-like receptors
  • Tuberculosis
  • Infection
  • Antimicrobial activity
  • Oxidative stress
  • Macrophages

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-61779-888-7_4
  • Chapter length: 26 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   219.00
Price excludes VAT (USA)
  • ISBN: 978-1-61779-888-7
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   279.99
Price excludes VAT (USA)
Hardcover Book
USD   279.99
Price excludes VAT (USA)
Fig. 4.1

References

  1. Kappelman J, Alcicek MC, Kazanci N, Schultz M, Ozkul M, Sen S. First Homo erectus from Turkey and implications for migrations into temperate Eurasia. Am J Phys Anthropol. 2008;135(1):110–6.

    PubMed  Google Scholar 

  2. Raviglione MC. The TB epidemic from 1992 to 2002. Tuberculosis (Edinb). 2003;83(1–3):4–14.

    Google Scholar 

  3. Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Arch Intern Med. 2003;163(9):1009–21.

    PubMed  Google Scholar 

  4. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project. JAMA. 1999;282(7):677–86.

    PubMed  CAS  Google Scholar 

  5. Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368(9547):1575–80.

    PubMed  Google Scholar 

  6. Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 1999;285(5428):732–6.

    PubMed  CAS  Google Scholar 

  7. Krutzik SR, Tan B, Li H, et al. TLR activation triggers the rapid differentiation of monocytes into macrophages and dendritic cells. Nat Med. 2005;11(6):653–60.

    PubMed  CAS  Google Scholar 

  8. Hertz CJ, Kiertscher SM, Godowski PJ, et al. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J Immunol. 2001;166(4):2444–50.

    PubMed  CAS  Google Scholar 

  9. Thoma-Uszynski S, Stenger S, Takeuchi O, et al. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science. 2001;291(5508):1544–7.

    PubMed  CAS  Google Scholar 

  10. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.

    PubMed  CAS  Google Scholar 

  11. Reiling N, Holscher C, Fehrenbach A, et al. Cutting edge: Toll-like receptor (TLR)2- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J Immunol. 2002;169(7):3480–4.

    PubMed  CAS  Google Scholar 

  12. Drennan MB, Nicolle D, Quesniaux VJ, et al. Toll-like receptor 2-deficient mice succumb to Mycobacterium tuberculosis infection. Am J Pathol. 2004;164(1):49–57.

    PubMed  CAS  Google Scholar 

  13. Bafica A, Scanga CA, Feng CG, Leifer C, Cheever A, Sher A. TLR9 regulates Th1 responses and cooperates with TLR2 in mediating optimal resistance to Mycobacterium tuberculosis. J Exp Med. 2005;202(12):1715–24.

    PubMed  CAS  Google Scholar 

  14. Ogus AC, Yoldas B, Ozdemir T, et al. The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease. Eur Respir J. 2004;23(2):219–23.

    PubMed  CAS  Google Scholar 

  15. Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellagi K. Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol. 2004;11(3):625–6.

    PubMed  CAS  Google Scholar 

  16. Yim JJ, Lee HW, Lee HS, et al. The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun. 2006;7(2):150–5.

    PubMed  CAS  Google Scholar 

  17. Bornman L, Campbell SJ, Fielding K, et al. Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study. J Infect Dis. 2004;190(9):1631–41.

    PubMed  CAS  Google Scholar 

  18. Bellamy R, Ruwende C, Corrah T, et al. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis. 1999;179(3):721–4.

    PubMed  CAS  Google Scholar 

  19. Selvaraj P, Narayanan PR, Reetha AM. Association of vitamin D receptor genotypes with the susceptibility to pulmonary tuberculosis in female patients & resistance in female contacts. Indian J Med Res. 2000;111:172–9.

    PubMed  CAS  Google Scholar 

  20. Liu W, Cao WC, Zhang CY, et al. VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: a case-control study. Int J Tuberc Lung Dis. 2004;8(4):428–34.

    PubMed  CAS  Google Scholar 

  21. Wilkinson RJ, Llewelyn M, Toossi Z, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet. 2000;355(9204):618–21.

    PubMed  CAS  Google Scholar 

  22. Hertting O, Holm A, Luthje P, et al. Vitamin D induction of the human antimicrobial peptide cathelicidin in the urinary bladder. PLoS One. 2010;5(12):e15580.

    PubMed  CAS  Google Scholar 

  23. Leszczynska K, Namiot A, Fein DE, et al. Bactericidal activities of the cationic steroid CSA-13 and the cathelicidin peptide LL-37 against Helicobacter pylori in simulated gastric juice. BMC Microbiol. 2009;9:187.

    PubMed  Google Scholar 

  24. McMahon L, Schwartz K, Yilmaz O, Brown E, Ryan LK, Diamond G. Vitamin D-mediated induction of innate immunity in gingival epithelial cells. Infect Immun. 2011;79(6):2250–6.

    PubMed  CAS  Google Scholar 

  25. Janeway Jr CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):1–13.

    PubMed  CAS  Google Scholar 

  26. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996;86(6):973–83.

    PubMed  CAS  Google Scholar 

  27. Meister M, Lemaitre B, Hoffmann JA. Antimicrobial peptide defense in Drosophila. Bioessays. 1997;19(11):1019–26.

    PubMed  CAS  Google Scholar 

  28. Medzhitov R, Preston-Hurlburt P, Janeway Jr CA. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7.

    PubMed  CAS  Google Scholar 

  29. Yang Y, Yin C, Pandey A, Abbott D, Sassetti C, Kelliher MA. NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2. J Biol Chem. 2007;282(50):36223–9.

    PubMed  CAS  Google Scholar 

  30. Girardin SE, Boneca IG, Viala J, et al. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 2003;278(11):8869–72.

    PubMed  CAS  Google Scholar 

  31. Delbridge LM, O’Riordan MX. Innate recognition of intracellular bacteria. Curr Opin Immunol. 2007;19(1):10–6.

    PubMed  CAS  Google Scholar 

  32. Zhang D, Zhang G, Hayden MS, et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303(5663):1522–6.

    PubMed  CAS  Google Scholar 

  33. Dunne A, O’Neill LA. Adaptor usage and Toll-like receptor signaling specificity. FEBS Lett. 2005;579(15):3330–5.

    PubMed  CAS  Google Scholar 

  34. Takeuchi O, Sato S, Horiuchi T, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169(1):10–4.

    PubMed  CAS  Google Scholar 

  35. Doyle SE, O’Connell RM, Miranda GA, et al. Toll-like receptors induce a phagocytic gene program through p38. J Exp Med. 2004;199(1):81–90.

    PubMed  CAS  Google Scholar 

  36. Blander JM, Medzhitov R. Regulation of phagosome maturation by signals from toll-like receptors. Science. 2004;304(5673):1014–8.

    PubMed  CAS  Google Scholar 

  37. Hertz CJ, Wu Q, Porter EM, et al. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human beta defensin-2. J Immunol. 2003;171(12):6820–6.

    PubMed  CAS  Google Scholar 

  38. Birchler T, Seibl R, Buchner K, et al. Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur J Immunol. 2001;31(11):3131–7.

    PubMed  CAS  Google Scholar 

  39. Doyle S, Vaidya S, O’Connell R, et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program. Immunity. 2002;17(3):251–63.

    PubMed  CAS  Google Scholar 

  40. Kawai T, Takeuchi O, Fujita T, et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001;167(10):5887–94.

    PubMed  CAS  Google Scholar 

  41. Kawai T, Sato S, Ishii KJ, et al. Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat Immunol. 2004;5(10):1061–8.

    PubMed  CAS  Google Scholar 

  42. Schmidt HH, Hofmann H, Schindler U, Shutenko ZS, Cunningham DD, Feelisch M. No.NO from NO synthase. Proc Natl Acad Sci USA. 1996;93(25):14492–7.

    PubMed  CAS  Google Scholar 

  43. Leber JH, Crimmins GT, Raghavan S, Meyer-Morse NP, Cox JS, Portnoy DA. Distinct TLR- and NLR-mediated transcriptional responses to an intracellular pathogen. PLoS Pathog. 2008;4(1):e6.

    PubMed  Google Scholar 

  44. Ferwerda G, Girardin SE, Kullberg BJ, et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog. 2005;1(3):279–85.

    PubMed  CAS  Google Scholar 

  45. Gandotra S, Jang S, Murray PJ, Salgame P, Ehrt S. Nucleotide-binding oligomerization domain protein 2-deficient mice control infection with Mycobacterium tuberculosis. Infect Immun. 2007;75(11):5127–34.

    PubMed  CAS  Google Scholar 

  46. Divangahi M, Mostowy S, Coulombe F, et al. NOD2-deficient mice have impaired resistance to Mycobacterium tuberculosis infection through defective innate and adaptive immunity. J Immunol. 2008;181(10):7157–65.

    PubMed  CAS  Google Scholar 

  47. Austin CM, Ma X, Graviss EA. Common nonsynonymous polymorphisms in the NOD2 gene are associated with resistance or susceptibility to tuberculosis disease in African Americans. J Infect Dis. 2008;197(12):1713–6.

    PubMed  CAS  Google Scholar 

  48. Stockton JC, Howson JM, Awomoyi AA, McAdam KP, Blackwell JM, Newport MJ. Polymorphism in NOD2, Crohn’s disease, and susceptibility to pulmonary tuberculosis. FEMS Immunol Med Microbiol. 2004;41(2):157–60.

    PubMed  CAS  Google Scholar 

  49. Wang TT, Dabbas B, Laperriere D, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem. 2010;285(4):2227–31.

    PubMed  CAS  Google Scholar 

  50. Cantorna MT. Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol. 2006;92(1):60–4.

    PubMed  CAS  Google Scholar 

  51. Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J. 2001;15(14):2579–85.

    PubMed  CAS  Google Scholar 

  52. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin Invest. 2006;116(8):2062–72.

    PubMed  CAS  Google Scholar 

  53. Rook GA, Steele J, Fraher L, et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology. 1986;57(1):159–63.

    PubMed  CAS  Google Scholar 

  54. Crowle AJ, Ross EJ, May MH. Inhibition by 1,25(OH)2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun. 1987;55(12):2945–50.

    PubMed  CAS  Google Scholar 

  55. Sly LM, Lopez M, Nauseef WM, Reiner NE. 1alpha,25-Dihydroxyvitamin D3-induced monocyte antimycobacterial activity is regulated by phosphatidylinositol 3-kinase and mediated by the NADPH-dependent phagocyte oxidase. J Biol Chem. 2001;276(38):35482–93.

    PubMed  CAS  Google Scholar 

  56. Anand PK, Kaul D. Downregulation of TACO gene transcription restricts mycobacterial entry/survival within human macrophages. FEMS Microbiol Lett. 2005;250(1):137–44.

    PubMed  CAS  Google Scholar 

  57. Anand PK, Kaul D. Vitamin D3-dependent pathway regulates TACO gene transcription. Biochem Biophys Res Commun. 2003;310(3):876–7.

    PubMed  CAS  Google Scholar 

  58. Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173(5):2909–12.

    PubMed  CAS  Google Scholar 

  59. Gombart AF, Borregaard N, Koeffler HP. 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 J. 2005;19(9):1067–77.

    PubMed  CAS  Google Scholar 

  60. Liu PT, Stenger S, Tang DH, Modlin RL. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007;179(4):2060–3.

    PubMed  CAS  Google Scholar 

  61. Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem. 2003;88(2):227–33.

    PubMed  CAS  Google Scholar 

  62. D’Ambrosio D, Cippitelli M, Cocciolo MG, et al. Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest. 1998;101(1):252–62.

    PubMed  Google Scholar 

  63. Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R. Dendritic cell modulation by 1alpha,25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc Natl Acad Sci USA. 2001;98(12):6800–5.

    PubMed  CAS  Google Scholar 

  64. Hewison M, Gacad MA, Lemire J, Adams JS. Vitamin D as a cytokine and hematopoetic factor. Rev Endocr Metab Disord. 2001;2(2):217–27.

    PubMed  CAS  Google Scholar 

  65. Lemire JM. Immunomodulatory actions of 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 1995;53(1–6):599–602.

    PubMed  CAS  Google Scholar 

  66. Panda DK, Miao D, Tremblay ML, et al. Targeted ablation of the 25-hydroxyvitamin D 1alpha-hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci USA. 2001;98(13):7498–503.

    PubMed  CAS  Google Scholar 

  67. Dardenne O, Prud’homme J, Arabian A, Glorieux FH, St-Arnaud R. Targeted inactivation of the 25-hydroxyvitamin D(3)-1(alpha)-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets. Endocrinology. 2001;142(7):3135–41.

    PubMed  CAS  Google Scholar 

  68. Hoover DM, Boulegue C, Yang D, et al. The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins. J Biol Chem. 2002;277(40):37647–54.

    PubMed  CAS  Google Scholar 

  69. Niyonsaba F, Ogawa H, Nagaoka I. Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology. 2004;111(3):273–81.

    PubMed  CAS  Google Scholar 

  70. Biragyn A, Ruffini PA, Leifer CA, et al. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science. 2002;298(5595):1025–9.

    PubMed  CAS  Google Scholar 

  71. Ganz T. Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 2003;3(9):710–20.

    PubMed  CAS  Google Scholar 

  72. Oppenheim JJ, Biragyn A, Kwak LW, Yang D. Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann Rheum Dis. 2003;62 Suppl 2:ii17–21.

    PubMed  CAS  Google Scholar 

  73. Hoover DM, Rajashankar KR, Blumenthal R, et al. The structure of human beta-defensin-2 shows evidence of higher order oligomerization. J Biol Chem. 2000;275(42):32911–8.

    PubMed  CAS  Google Scholar 

  74. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol. 2004;75(1):39–48.

    PubMed  Google Scholar 

  75. Ahmad I, Perkins WR, Lupan DM, Selsted ME, Janoff AS. Liposomal entrapment of the neutrophil-derived peptide indolicidin endows it with in vivo antifungal activity. Biochim Biophys Acta. 1995;1237(2):109–14.

    PubMed  Google Scholar 

  76. Shin SY, Kang SW, Lee DG, Eom SH, Song WK, Kim JI. CRAMP analogues having potent antibiotic activity against bacterial, fungal, and tumor cells without hemolytic activity. Biochem Biophys Res Commun. 2000;275(3):904–9.

    PubMed  CAS  Google Scholar 

  77. Giacometti A, Cirioni O, Barchiesi F, Caselli F, Scalise G. In-vitro activity of polycationic peptides against Cryptosporidium parvum, Pneumocystis carinii and yeast clinical isolates. J Antimicrob Chemother. 1999;44(3):403–6.

    PubMed  CAS  Google Scholar 

  78. Cirioni O, Giacometti A, Barchiesi F, Scalise G. In-vitro activity of lytic peptides alone and in combination with macrolides and inhibitors of dihydrofolate reductase against Pneumocystis carinii. J Antimicrob Chemother. 1998;42(4):445–51.

    PubMed  CAS  Google Scholar 

  79. Tamamura H, Murakami T, Horiuchi S, et al. Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity. Chem Pharm Bull(Tokyo). 1995;43(5):853–8.

    CAS  Google Scholar 

  80. Bals R, Wang X, Zasloff M, Wilson JM. The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface. Proc Natl Acad Sci USA. 1998;95(16):9541–6.

    PubMed  CAS  Google Scholar 

  81. Meyer T, Stockfleth E, Christophers E. Immune response profiles in human skin. Br J Dermatol. 2007;157 Suppl 2:1–7.

    PubMed  CAS  Google Scholar 

  82. Sorensen O, Arnljots K, Cowland JB, Bainton DF, Borregaard N. The human antibacterial cathelicidin, hCAP-18, is synthesized in myelocytes and metamyelocytes and localized to specific granules in neutrophils. Blood. 1997;90(7):2796–803.

    PubMed  CAS  Google Scholar 

  83. Di NA, Vitiello A, Gallo RL. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J Immunol. 2003;170(5):2274–8.

    Google Scholar 

  84. Agerberth B, Charo J, Werr J, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96(9):3086–93.

    PubMed  CAS  Google Scholar 

  85. Martineau AR, Wilkinson KA, Newton SM, et al. IFN-gamma- and TNF-independent vitamin D-inducible human suppression of mycobacteria: the role of cathelicidin LL-37. J Immunol. 2007;178(11):7190–8.

    PubMed  CAS  Google Scholar 

  86. Rivas-Santiago B, Schwander SK, Sarabia C, et al. Human {beta}-defensin 2 is expressed and associated with Mycobacterium tuberculosis during infection of human alveolar epithelial cells. Infect Immun. 2005;73(8):4505–11.

    PubMed  CAS  Google Scholar 

  87. Sow FB, Florence WC, Satoskar AR, Schlesinger LS, Zwilling BS, Lafuse WP. Expression and localization of hepcidin in macrophages: a role in host defense against tuberculosis. J Leukoc Biol. 2007;82(4):934–45.

    PubMed  CAS  Google Scholar 

  88. Nathan C, Shiloh MU. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA. 2000;97(16):8841–8.

    PubMed  CAS  Google Scholar 

  89. Clark RA, Leidal KG, Pearson DW, Nauseef WM. NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system. J Biol Chem. 1987;262(9):4065–74.

    PubMed  CAS  Google Scholar 

  90. Borregaard N, Heiple JM, Simons ER, Clark RA. Subcellular localization of the b-cytochrome component of the human neutrophil microbicidal oxidase: translocation during activation. J Cell Biol. 1983;97(1):52–61.

    PubMed  CAS  Google Scholar 

  91. Fang FC. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat Rev Microbiol. 2004;2(10):820–32.

    PubMed  CAS  Google Scholar 

  92. Tosi MF. Innate immune responses to infection. J Allergy Clin Immunol. 2005;116(2):241–9.

    PubMed  CAS  Google Scholar 

  93. Cadwallader KA, Condliffe AM, McGregor A, et al. Regulation of phosphatidylinositol 3-kinase activity and phosphatidylinositol 3,4,5-trisphosphate accumulation by neutrophil priming agents. J Immunol. 2002;169(6):3336–44.

    PubMed  CAS  Google Scholar 

  94. Levy R, Malech HL. Effect of 1,25-dihydroxyvitamin D3, lipopolysaccharide, or lipoteichoic acid on the expression of NADPH oxidase components in cultured human monocytes. J Immunol. 1991;147(9):3066–71.

    PubMed  CAS  Google Scholar 

  95. Cassatella MA, Bazzoni F, Flynn RM, Dusi S, Trinchieri G, Rossi F. Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components. J Biol Chem. 1990;265(33):20241–6.

    PubMed  CAS  Google Scholar 

  96. Li H, Poulos TL. Structure-function studies on nitric oxide synthases. J Inorg Biochem. 2005;99(1):293–305.

    PubMed  CAS  Google Scholar 

  97. Bogdan C, Rollinghoff M, Diefenbach A. The role of nitric oxide in innate immunity. Immunol Rev. 2000;173:17–26.

    PubMed  CAS  Google Scholar 

  98. Hurshman AR, Krebs C, Edmondson DE, Huynh BH, Marletta MA. Formation of a pterin radical in the reaction of the heme domain of inducible nitric oxide synthase with oxygen. Biochemistry. 1999;38(48):15689–96.

    PubMed  CAS  Google Scholar 

  99. Schapiro JM, Libby SJ, Fang FC. Inhibition of bacterial DNA replication by zinc mobilization during nitrosative stress. Proc Natl Acad Sci USA. 2003;100(14):8496–501.

    PubMed  CAS  Google Scholar 

  100. Pacelli R, Wink DA, Cook JA, et al. Nitric oxide potentiates hydrogen peroxide-induced killing of Escherichia coli. J Exp Med. 1995;182(5):1469–79.

    PubMed  CAS  Google Scholar 

  101. Stevanin TM, Ioannidis N, Mills CE, Kim SO, Hughes MN, Poole RK. Flavohemoglobin Hmp affords inducible protection for Escherichia coli respiration, catalyzed by cytochromes bo’ or bd, from nitric oxide. J Biol Chem. 2000;275(46):35868–75.

    PubMed  CAS  Google Scholar 

  102. Lepoivre M, Fieschi F, Coves J, Thelander L, Fontecave M. Inactivation of ribonucleotide reductase by nitric oxide. Biochem Biophys Res Commun. 1991;179(1):442–8.

    PubMed  CAS  Google Scholar 

  103. Wink DA, Kasprzak KS, Maragos CM, et al. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science. 1991;254(5034):1001–3.

    PubMed  CAS  Google Scholar 

  104. Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR. The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res. 1999;424(1–2):37–49.

    PubMed  CAS  Google Scholar 

  105. Spek EJ, Wright TL, Stitt MS, et al. Recombinational repair is critical for survival of Escherichia coli exposed to nitric oxide. J Bacteriol. 2001;183(1):131–8.

    PubMed  CAS  Google Scholar 

  106. Evans TJ, Buttery LD, Carpenter A, Springall DR, Polak JM, Cohen J. Cytokine-treated human neutrophils contain inducible nitric oxide synthase that produces nitration of ingested bacteria. Proc Natl Acad Sci USA. 1996;93(18):9553–8.

    PubMed  CAS  Google Scholar 

  107. Xie QW, Kashiwabara Y, Nathan C. Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem. 1994;269(7):4705–8.

    PubMed  CAS  Google Scholar 

  108. Kamijo R, Harada H, Matsuyama T, et al. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science. 1994;263(5153):1612–5.

    PubMed  CAS  Google Scholar 

  109. Taylor BS, Geller DA. Molecular regulation of the human inducible nitric oxide synthase (iNOS) gene. Shock. 2000;13(6):413–24.

    PubMed  CAS  Google Scholar 

  110. Watkins SC, Macaulay W, Turner D, Kang R, Rubash HE, Evans CH. Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses. Am J Pathol. 1997;150(4):1199–206.

    PubMed  CAS  Google Scholar 

  111. Chen F, Kuhn DC, Gaydos LJ, Demers LM. Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells. Acta Pathol Microbiol Immunol Scand. 1996;104(3):176–82.

    CAS  Google Scholar 

  112. Jagannath C, Actor JK, Hunter Jr RL. Induction of nitric oxide in human monocytes and monocyte cell lines by Mycobacterium tuberculosis. Nitric Oxide. 1998;2(3):174–86.

    PubMed  CAS  Google Scholar 

  113. Baek SH, Kwon TK, Lim JH, et al. Secretory phospholipase A2-potentiated inducible nitric oxide synthase expression by macrophages requires NF-kappa B activation. J Immunol. 2000;164(12):6359–65.

    PubMed  CAS  Google Scholar 

  114. Weinberg JB, Misukonis MA, Shami PJ, et al. Human mononuclear phagocyte inducible nitric oxide synthase (iNOS): analysis of iNOS mRNA, iNOS protein, biopterin, and nitric oxide production by blood monocytes and peritoneal macrophages. Blood. 1995;86(3):1184–95.

    PubMed  CAS  Google Scholar 

  115. Adams JS, Ren SY, Arbelle JE, Shany S, Gacad MA. Coordinate regulation of nitric oxide and 1,25-dihydroxyvitamin D production in the avian myelomonocytic cell line HD-11. Endocrinology. 1995;136(5):2262–9.

    PubMed  CAS  Google Scholar 

  116. Adams JS, Ren SY. Autoregulation of 1,25-dihydroxyvitamin D synthesis in macrophage mitochondria by nitric oxide. Endocrinology. 1996;137(10):4514–7.

    PubMed  CAS  Google Scholar 

  117. Chang JM, Kuo MC, Kuo HT, et al. 1-alpha,25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells. J Lab Clin Med. 2004;143(1):14–22.

    PubMed  CAS  Google Scholar 

  118. Garcion E, Sindji L, Montero-Menei C, Andre C, Brachet P, Darcy F. Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxyvitamin D3. Glia. 1998;22(3):282–94.

    PubMed  CAS  Google Scholar 

  119. Nelson CD, Reinhardt TA, Thacker TC, Beitz DC, Lippolis JD. Modulation of the bovine innate immune response by production of 1alpha,25-dihydroxyvitamin D(3) in bovine monocytes. J Dairy Sci. 2010;93(3):1041–9.

    PubMed  CAS  Google Scholar 

  120. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004;119(6):753–66.

    PubMed  CAS  Google Scholar 

  121. Alonso S, Pethe K, Russell DG, Purdy GE. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc Natl Acad Sci USA. 2007;104(14):6031–6.

    PubMed  CAS  Google Scholar 

  122. Yuk JM, Shin DM, Lee HM, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009;6(3):231–43.

    PubMed  CAS  Google Scholar 

  123. Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity. 2007;27(1):135–44.

    PubMed  CAS  Google Scholar 

  124. Delgado MA, Elmaoued RA, Davis AS, Kyei G, Deretic V. Toll-like receptors control autophagy. EMBO J. 2008;27(7):1110–21.

    PubMed  CAS  Google Scholar 

  125. Ravikumar M, Dheenadhayalan V, Rajaram K, et al. Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India. Tuber Lung Dis. 1999;79(5):309–17.

    PubMed  CAS  Google Scholar 

  126. Mehra NK, Rajalingam R, Mitra DK, Taneja V, Giphart MJ. Variants of HLA-DR2/DR51 group haplotypes and susceptibility to tuberculoid leprosy and pulmonary tuberculosis in Asian Indians. Int J Lepr Other Mycobact Dis. 1995;63(2):241–8.

    PubMed  CAS  Google Scholar 

  127. Amirzargar AA, Yalda A, Hajabolbaghi M, et al. The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis. Int J Tuberc Lung Dis. 2004;8(8):1017–21.

    PubMed  CAS  Google Scholar 

  128. Liu J, Fujiwara TM, Buu NT, et al. Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene. Am J Hum Genet. 1995;56(4):845–53.

    PubMed  CAS  Google Scholar 

  129. Jouanguy E, Lamhamedi-Cherradi S, Lammas D, et al. A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection. Nat Genet. 1999;21(4):370–8.

    PubMed  CAS  Google Scholar 

  130. Pan H, Yan BS, Rojas M, et al. Ipr1 gene mediates innate immunity to tuberculosis. Nature. 2005;434(7034):767–72.

    PubMed  CAS  Google Scholar 

  131. Fitness J, Floyd S, Warndorff DK, et al. Large-scale candidate gene study of leprosy susceptibility in the Karonga district of northern Malawi. Am J Trop Med Hyg. 2004;71(3):330–40.

    PubMed  CAS  Google Scholar 

  132. Grange JM, Davies PD, Brown RC, Woodhead JS, Kardjito T. A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis. Tubercle. 1985;66(3):187–91.

    PubMed  CAS  Google Scholar 

  133. Delgado JC, Baena A, Thim S, Goldfeld AE. Ethnic-specific genetic associations with pulmonary tuberculosis. J Infect Dis. 2002;186(10):1463–8.

    PubMed  CAS  Google Scholar 

  134. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP. Genetics and biology of vitamin D receptor polymorphisms. Gene. 2004;338(2):143–56.

    PubMed  CAS  Google Scholar 

  135. Hewison M, Freeman L, Hughes SV, et al. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol. 2003;170(11):5382–90.

    PubMed  CAS  Google Scholar 

  136. Hewison M, Burke F, Evans KN, et al. Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease. J Steroid Biochem Mol Biol. 2007;103(3–5):316–21.

    PubMed  CAS  Google Scholar 

  137. Yang S, Smith C, Prahl JM, Luo X, Deluca HF. Vitamin D deficiency suppresses cell-mediated immunity in vivo. Arch Biochem Biophys. 1993;303(1):98–106.

    PubMed  CAS  Google Scholar 

  138. Lathers DM, Clark JI, Achille NJ, Young MR. Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3. Cancer Immunol Immunother. 2004;53(5):422–30.

    PubMed  CAS  Google Scholar 

  139. Krutzik SR, Hewison M, Liu PT, et al. IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J Immunol. 2008;181(10):7115–20.

    PubMed  CAS  Google Scholar 

  140. Liu PT, Schenk M, Walker VP, et al. Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses. PLoS One. 2009;4(6):e5810.

    PubMed  Google Scholar 

  141. Wilkinson RJ, Patel P, Llewelyn M, et al. Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis. J Exp Med. 1999;189(12):1863–74.

    PubMed  CAS  Google Scholar 

  142. Fremond CM, Togbe D, Doz E, et al. IL-1 receptor-mediated signal is an essential component of MyD88-dependent innate response to Mycobacterium tuberculosis infection. J Immunol. 2007;179(2):1178–89.

    PubMed  CAS  Google Scholar 

  143. Barnes PF, Modlin RL, Bikle DD, Adams JS. Transpleural gradient of 1,25-dihydroxyvitamin D in tuberculous pleuritis. J Clin Invest. 1989;83(5):1527–32.

    PubMed  CAS  Google Scholar 

  144. Edfeldt K, Liu PT, Chun R, et al. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci USA. 2010;107(52):22593–8.

    Google Scholar 

  145. Hagenau T, Vest R, Gissel TN, et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos Int. 2009;20(1):133–40.

    PubMed  CAS  Google Scholar 

  146. Adams JS, Ren S, Liu PT, et al. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol. 2009;182(7):4289–95.

    PubMed  CAS  Google Scholar 

  147. Martineau AR, Wilkinson RJ, Wilkinson KA, et al. A single dose of vitamin D enhances immunity to mycobacteria. Am J Respir Crit Care Med. 2007;176(2):208–13.

    PubMed  CAS  Google Scholar 

  148. Shin DM, Yuk JM, Lee HM, et al. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signaling. Cell Microbiol. 2010;12(11):1648–65.

    PubMed  CAS  Google Scholar 

  149. Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase. Mol Cell Endocrinol. 2004;215(1–2):31–8.

    PubMed  CAS  Google Scholar 

  150. Hansdottir S, Monick MM, Hinde SL, Lovan N, Look DC, Hunninghake GW. Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense. J Immunol. 2008;181(10):7090–9.

    PubMed  CAS  Google Scholar 

  151. Ponchon G, Kennan AL, Deluca HF. “Activation” of vitamin D by the liver. J Clin Invest. 1969;48(11):2032–7.

    PubMed  CAS  Google Scholar 

  152. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86(2):888–94.

    PubMed  CAS  Google Scholar 

  153. Kreutz M, Andreesen R, Krause SW, Szabo A, Ritz E, Reichel H. 1,25-Dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood. 1993;82(4):1300–7.

    PubMed  CAS  Google Scholar 

  154. Sigmundsdottir H, Pan J, Debes GF, et al. DCs metabolize sunlight-induced vitamin D3 to ­‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007;8(3):285–93.

    PubMed  CAS  Google Scholar 

  155. Tangpricha V, Flanagan JN, Whitlatch LW, et al. 25-Hydroxyvitamin D-1[alpha]-hydroxylase in normal and malignant colon tissue. Lancet. 2001;357(9269):1673–4.

    PubMed  CAS  Google Scholar 

  156. Bikle DD, Nemanic MK, Gee E, Elias P. 1,25-Dihydroxyvitamin D3 production by human keratinocytes. Kinetics and regulation. J Clin Invest. 1986;78(2):557–66.

    PubMed  CAS  Google Scholar 

  157. Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117(3):803–11.

    PubMed  CAS  Google Scholar 

  158. Schwartz GG, Whitlatch LW, Chen TC, Lokeshwar BL, Holick MF. Human prostate cells synthesize 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3. Cancer Epidemiol Biomarkers Prev. 1998;7(5):391–5.

    PubMed  CAS  Google Scholar 

  159. Kemmis CM, Salvador SM, Smith KM, Welsh J. Human mammary epithelial cells express CYP27B1 and are growth inhibited by 25-hydroxyvitamin D-3, the major circulating form of vitamin D-3. J Nutr. 2006;136(4):887–92.

    PubMed  CAS  Google Scholar 

  160. Ritter M, Mennerich D, Weith A, Seither P. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C) on the regulation of Toll-like receptors, adaptor proteins and inflammatory response. J Inflamm (Lond). 2005;2:16.

    Google Scholar 

  161. Sha Q, Truong-Tran AQ, Plitt JR, Beck LA, Schleimer RP. Activation of airway epithelial cells by toll-like receptor agonists. Am J Respir Cell Mol Biol. 2004;31(3):358–64.

    PubMed  Google Scholar 

  162. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002;113(Suppl 1A):5S–13.

    PubMed  Google Scholar 

  163. Ronald A. The etiology of urinary tract infection: traditional and emerging pathogens. Dis Mon. 2003;49(2):71–82.

    PubMed  Google Scholar 

  164. Kimball SM, Ursell MR, O’Connor P, Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. Am J Clin Nutr. 2007;86(3):645–51.

    PubMed  CAS  Google Scholar 

  165. Schmausser B, Endrich S, Beier D, et al. Triggering receptor expressed on myeloid cells-1 (TREM-1) expression on gastric epithelium: implication for a role of TREM-1 in Helicobacter pylori infection. Clin Exp Immunol. 2008;152(1):88–94.

    PubMed  CAS  Google Scholar 

  166. Rigo I, McMahon L, Dhawan P, et al. Induction of triggering receptor expressed on myeloid cells (TREM-1) in airway epithelial cells by 1,25(OH)2 vitamin D3. Innate Immun. 2012;18(2):250–7.

    Google Scholar 

  167. Bonass WA, High AS, Owen PJ, Devine DA. Expression of beta-defensin genes by human salivary glands. Oral Microbiol Immunol. 1999;14(6):371–4.

    PubMed  CAS  Google Scholar 

  168. Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol. 2005;7(2):119–33.

    PubMed  CAS  Google Scholar 

  169. Dunsche A, Acil Y, Dommisch H, Siebert R, Schroder JM, Jepsen S. The novel human beta-defensin-3 is widely expressed in oral tissues. Eur J Oral Sci. 2002;110(2):121–4.

    PubMed  CAS  Google Scholar 

  170. Murakami M, Ohtake T, Dorschner RA, Gallo RL. Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res. 2002;81(12):845–50.

    PubMed  CAS  Google Scholar 

  171. Woo JS, Jeong JY, Hwang YJ, Chae SW, Hwang SJ, Lee HM. Expression of cathelicidin in human salivary glands. Arch Otolaryngol Head Neck Surg. 2003;129(2):211–4.

    PubMed  Google Scholar 

  172. Tao R, Jurevic RJ, Coulton KK, et al. Salivary antimicrobial peptide expression and dental caries experience in children. Antimicrob Agents Chemother. 2005;49(9):3883–8.

    PubMed  CAS  Google Scholar 

  173. Schroeder HE. The periodontium. Berlin: Springer; 1986.

    Google Scholar 

  174. Carlsson G, Wahlin YB, Johansson A, et al. Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia. J Periodontol. 2006;77(4):744–51.

    PubMed  Google Scholar 

  175. de Haar SF, Hiemstra PS, van Steenbergen MT, Everts V, Beertsen W. Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans. Infect Immun. 2006;74(9):5284–91.

    PubMed  Google Scholar 

  176. Altman H, Steinberg D, Porat Y, et al. In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria. J Antimicrob Chemother. 2006;58(1):198–201.

    PubMed  CAS  Google Scholar 

  177. Bragd L, Dahlen G, Wikstrom M, Slots J. The capability of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius to indicate progressive periodontitis; a retrospective study. J Clin Periodontol. 1987;14(2):95–9.

    PubMed  CAS  Google Scholar 

  178. Joly S, Maze C, McCray Jr PB, Guthmiller JM. Human beta-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol. 2004;42(3):1024–9.

    PubMed  CAS  Google Scholar 

  179. Nishimura E, Eto A, Kato M, et al. Oral streptococci exhibit diverse susceptibility to human beta-defensin-2: antimicrobial effects of hBD-2 on oral streptococci. Curr Microbiol. 2004;48(2):85–7.

    PubMed  CAS  Google Scholar 

  180. Tanaka D, Miyasaki KT, Lehrer RI. Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium. Oral Microbiol Immunol. 2000;15(4):226–31.

    PubMed  CAS  Google Scholar 

  181. Brown LM. Helicobacter pylori: epidemiology and routes of transmission. Epidemiol Rev. 2000;22(2):283–97.

    PubMed  CAS  Google Scholar 

  182. Lacy BE, Rosemore J. Helicobacter pylori: ulcers and more: the beginning of an era. J Nutr. 2001;131(10):2789S–93.

    PubMed  CAS  Google Scholar 

  183. Meyer JM, Silliman NP, Wang W, et al. Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993–1999. Ann Intern Med. 2002;136(1):13–24.

    PubMed  Google Scholar 

  184. Trieber CA, Taylor DE. Mutations in the 16 S rRNA genes of Helicobacter pylori mediate resistance to tetracycline. J Bacteriol. 2002;184(8):2131–40.

    PubMed  CAS  Google Scholar 

  185. Kawaura A, Takeda E, Tanida N, et al. Inhibitory effect of long term 1α-hydroxyvitamin D3 administration on Helicobacter pylori infection. J Clin Biochem Nutr. 2006;38(2):103–6.

    CAS  Google Scholar 

  186. Dowling GB, Thomas EW. Treatment of lupus vulgaris with calciferol. Lancet. 1946;22:919–23.

    Google Scholar 

  187. Morcos MM, Gabr AA, Samuel S, et al. Vitamin D administration to tuberculous children and its value. Boll Chim Farm. 1998;137(5):157–64.

    PubMed  CAS  Google Scholar 

  188. Nursyam EW, Amin Z, Rumende CM. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones. 2006;38(1):3–5.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Philip T. Liu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Vazirnia, A., Liu, P.T. (2012). Vitamin D and the Innate Immune Response. In: Litonjua, A. (eds) Vitamin D and the Lung. Respiratory Medicine, vol 3. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-888-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-888-7_4

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-887-0

  • Online ISBN: 978-1-61779-888-7

  • eBook Packages: MedicineMedicine (R0)