Although this is with a different intracellular pathogen than Cpn, it suggests one of the possible protective mechanisms that Vitamin D gives against intracellular pathogens. Like Cpn, Mycobacterium tuberculosis infects the immune cells (macrophages) themselves, and this study describes the inhibition of cell invasion by Vitamin D. J Microbiol Immunol Infect. 2008 Feb;41(1):17-25. Synergistic action of vitamin D and retinoic acid restricts invasion of macrophages by pathogenic mycobacteria. Anand PK, Kaul D, Sharma M. Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. 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.