Skip to main content
SpringerLink
Log in

Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis infection in mice

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

The aim of the study is to investigate the immunological changes after stimulation with bacillus Calmette–Guerin (BCG) in mice with vitamin D deficiency. After weaning, mice were divided into the vitamin D-deficient group (−D group), the normal group (N group), and the vitamin D-supplemented group (+D group). Twelve-week-old mice were intraperitoneally injected with 0.5 mg/ml BCG (≥1.0 × 106 CFU/mg) and maintained for 6 weeks. Spleen lymphocytes were isolated, and the percentages of CD4+ and CD8+ lymphocytes were determined by flow cytometry. IFN-γ levels, IL-10 levels, and the TB-PPD-specific antibody titer were determined by ELISA. The inter-group difference was analyzed using one-way ANOVA, and multiple comparisons were analyzed using the LSD test. The percentage of CD4+ cells was 27.1 ± 0.6 in the −D group, 23.62 ± 0.42 in the N group, and 19.46 ± 0.32 in the +D group (P < 0.05). The percentage of CD8+ lymphocytes was 12.15 ± 0.61 in the −D group, 8.7 ± 0.64 in the N group, and 7.12 ± 0.48 in the +D group (P < 0.05). The CD4+/CD8+ ratio was 2.23 ± 0.15 in the −D group, 2.71 ± 0.21 in the N group, and 2.73 ± 0.31 in the +D group (P < 0.05). The plasma IFN-γ levels were 416.42 ± 16.42 pg/ml in the −D group, 325.41 ± 11.16 pg/ml in the N group, and 276.26 ± 25.32 pg/ml in the +D group (P < 0.005). The plasma IL-10 levels were 16.45 ± 1.58 pg/ml in the −D group, 24.31 ± 2.16 pg/ml in the N group, and 26.28 ± 0.42 pg/ml in the +D group (P < 0.005). The serum TB-PPD-specific antibody level was significantly higher in the −D group than in the N and +D groups. Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis infection in mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. North RJ, Jung YJ (2004) Immunity to tuberculosis. Annu Rev Immunol 22:599–623

    Article  PubMed  CAS  Google Scholar 

  2. Zasloff M (2006) Fighting infections with vitamin D. Nat Med 12:388–390

    Article  PubMed  CAS  Google Scholar 

  3. Goswami R, Mishra SK, Kochupillai N (2008) Prevalence and potential significance of vitamin D deficiency in Asian Indians. Indian J Med Res 127:229–238

    PubMed  CAS  Google Scholar 

  4. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496

    Article  PubMed  CAS  Google Scholar 

  5. Morcos MM, Gabr AA, Samuel S, Kamel M, el Baz M, el Beshry M et al (1998) Vitamin D administration to tuberculous children and its value. Boll Chim Farm 137:157–164

    PubMed  CAS  Google Scholar 

  6. Toubi E, Shoenfeld Y (2010) The role of vitamin D in regulating immune responses. IMAJ 12:174–175

    PubMed  Google Scholar 

  7. Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Clin N Am 39:365–379

    CAS  Google Scholar 

  8. Martineau AR, Wilkinson RJ, Wilkinson KA, Newton SM, Kampmann B, Hall BM et al (2007) A single dose of vitamin D enhances immunity to mycobacteria. Trial. Am J Respir Crit Care Med 176:208–213

    Article  PubMed  CAS  Google Scholar 

  9. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM et al (2009) Vitamin D as supplementary treatment for tuberculosis a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 179:843–850

    Article  PubMed  CAS  Google Scholar 

  10. Bikle DD (2008) Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens 179:348–352

    Article  Google Scholar 

  11. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR et al (2006) Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science 311:1770–1773

    Article  PubMed  CAS  Google Scholar 

  12. Rook GA, Steele J, Fraher L, Barker S, Karmali R, O’Riordan J, Stanford J (1986) Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57(1):159–163

    PubMed  CAS  Google Scholar 

  13. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH (2004) Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 173(5):2909–2912

    PubMed  CAS  Google Scholar 

  14. Islam D, Bandholtz L, Nilsson J, Wigzell H, Christensson B, Agerberth B, Gudmundsson G (2001) Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator. Nat Med 7(2):180–185

    Article  PubMed  CAS  Google Scholar 

  15. Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zügel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A (2006) Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 36(2):361–370

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. Malley RC, Muller HK, Norval M, Woods GM (2009) Vitamin D3 deficiency enhances contact hypersensitivity in male but not in female mice. Cell Immunol 255(1–2):33–40 Epub 2008 Nov 13

    Article  PubMed  CAS  Google Scholar 

  18. Misharin A, Hewison M, Chen CR, Lagishetty V, Aliesky HA, Mizutori Y, Rapoport B, McLachlan SM (2009) Vitamin D deficiency modulates Graves’ hyperthyroidism induced in BALB/c mice by thyrotropin receptor immunization. Endocrinology 150(2):1051–1060

    Article  PubMed  CAS  Google Scholar 

  19. Pichugin AV, Petrovskaya SN (2006) Apt AS.H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens. J Leukoc Biol 79(4):739–746 Epub 2006 Jan 13

    Article  PubMed  CAS  Google Scholar 

  20. Lemire JM (1991) Archer DC.1,25-dihydroxyvitamin D3 prevents the in vivo induction of murine experimental autoimmune encephalomyelitis. J Clin Invest 87(3):1103–1107

    Article  PubMed  CAS  Google Scholar 

  21. Cantorna MT, Woodward WD, Hayes CE (1998) DeLuca HF.1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. J Immunol 160(11):5314–5319

    PubMed  CAS  Google Scholar 

  22. Adams JS, Hewison M (2008) Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 4(2):80–90

    Article  PubMed  CAS  Google Scholar 

  23. Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM, O’Garra A (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 195(5):603–616

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Orthopedic Surgery, Southwest Hospital, Third Military Medical University, Gaotanyan Str. 30, Chongqing, 400038, People’s Republic of China

    Hui-feng Yang, Ze-hua Zhang, Zheng-qi Chang, Kang-lai Tang, De-zhi Lin & Jian-zhong Xu

Authors
  1. Hui-feng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ze-hua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zheng-qi Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kang-lai Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. De-zhi Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian-zhong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian-zhong Xu.

Additional information

Hui-feng Yang and Ze-hua Zhang contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yang, Hf., Zhang, Zh., Chang, Zq. et al. Vitamin D deficiency affects the immunity against Mycobacterium tuberculosis infection in mice. Clin Exp Med 13, 265–270 (2013). https://doi.org/10.1007/s10238-012-0204-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-012-0204-7

Keywords

Search

Navigation