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. 2012 Oct;8(10):1523-5.
doi: 10.4161/auto.21154. Epub 2012 Aug 15.

Autophagy induction by vitamin D inhibits both Mycobacterium tuberculosis and human immunodeficiency virus type 1

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Autophagy induction by vitamin D inhibits both Mycobacterium tuberculosis and human immunodeficiency virus type 1

Grant R Campbell et al. Autophagy. 2012 Oct.

Abstract

Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We report that physiological concentrations of 1α,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits M. tuberculosis and HIV replication in co-infected macrophages through human cathelicidin microbial peptide-dependent autophagy that requires phagosomal maturation. These findings provide a biological explanation for the importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections.

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Figures

Figure 1.
Figure 1.
The role of autophagy and CAMP in 1,25D3-mediated inhibition of Mtb and HIV. HIV budding occurs into the multivesicular endosomes of macrophages. Mtb enters through phagocytosis. Cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1) 1α-hydroxylates the inactive 25D3 into the active 1,25D3. 1,25D3 induces the expression of CAMP presumably through binding to the vitamin D (1,25D3) receptor (VDR), which heterodimerizes with the retinoid X receptor (RXR) and directly regulates transcription by binding to the vitamin D response element (VDRE) consensus sequence located upstream of the Camp gene. The expression of CAMP is required both for autophagosome and phagolysosome biogenesis, which leads to killing of the microbial pathogens through autophagy. Adapted from Jo EK. Innate immunity to mycobacteria: vitamin D and autophagy. Cell Microbiol 2010; 12:1026–35; 10.1111/j.1462-5822.2010.01491.x.

Comment on

  • Campbell GR, Spector SA. Vitamin D Inhibits Human Immunodeficiency Virus Type 1 and Mycobacterium tuberculosis Infection in Macrophages through the Induction of Autophagy. PLoS Pathog. 2012;8:e1002689. doi: 10.1371/journal.ppat.1002689.

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