Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria

J Microbiol Immunol Infect. 2008 Feb;41(1):17-25.


Background and purpose: Phagosomal maturation arrest is known to play a central role in the survival of pathogenic mycobacteria within macrophages. The maturation arrest of mycobacterial phagosome results from the retention of tryptophan-aspartate-containing coat protein (TACO) on this organelle, enabling successful replication of the pathogen. We have shown earlier that vitamin D(3) and retinoic acid (RA) down-regulate TACO gene transcription in a dose-dependent manner.

Methods: In this study, we analyzed the promoter region of TACO gene using bioinformatics tools and observed that the vitamin D receptor (VDR)/retinoid-X-receptor (RXR) response sequence was highly functional. We also evaluated the effect of treatment with vitamin D(3)/RA on Mycobacterium tuberculosis entry and survival in cultured human macrophages.

Results: TACO gene down-regulation observed with vitamin D(3)/RA treatment occurred through modulation of this gene via the VDR/RXR response sequence present in the promoter region of TACO gene. Treatment of macrophages with vitamin D(3)/RA allows maturation of mycobacterial phagosome, leading to degradation of the pathogen.

Conclusions: Our results elucidate the mechanism of TACO gene down-regulation observed with vitamin D(3)/RA. Furthermore, the results revealed that vitamin D(3)/RA treatment inhibits mycobacterial entry as well as survival within macrophages, possibly through rescue of phagosome maturation arrest. The developing knowledge in this area suggests that vitamin D(3)/RA may be of importance in the treatment of intracellular infection, particularly tuberculosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line, Tumor
  • Down-Regulation*
  • Genes, Reporter
  • Humans
  • Macrophages / cytology
  • Macrophages / immunology
  • Macrophages / microbiology*
  • Microbial Viability / drug effects
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Mycobacterium tuberculosis / physiology*
  • Phagocytosis
  • Response Elements
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Vitamin D / metabolism*
  • Vitamin D / pharmacology


  • Microfilament Proteins
  • Transcription Factors
  • Vitamin D
  • coronin proteins
  • Tretinoin