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Volume 41, Number 1, February 2008

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


Paras K. Anand, Deepak Kaul, Meera Sharma
Molecular Biology Unit, Department of Experimental Medicine and Biotechnology and Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Received: February 8, 2006    Revised: September 1, 2006    Accepted: September 13, 2006   

 

Corresponding author:

Dr. Deepak Kaul, Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh 160 012, India. E-mail: Dr. Deepak Kaul This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

 



 

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 D3 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 D3/RA on Mycobacterium tuberculosis entry and survival in cultured human macrophages.

 



 

Results:

TACO gene down-regulation observed with vitamin D3/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 D3/RA allows maturation of mycobacterial phagosome, leading to degradation of the pathogen.

 



 

Conclusion:

Our results elucidate the mechanism of TACO gene down-regulation observed with vitamin D3/RA. Furthermore, the results revealed that vitamin D3/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 D3/RA may be of importance in the treatment of intracellular infection, particularly tuberculosis.

 



 

Key words:

Down-regulation; DNA-binding proteins; Macrophages; Mycobacterium tuberculosis; Tretinoin; Vitamin D


 



 

J Microbiol Immunol Infect. 2008;41:17-25.