Vitamin D and the innate immune response

Abstract

Active vitamin D metabolites play a major role in key functions of the innate immune response. Triggering of the vitamin D receptor (VDR) by those metabolites has been demonstrated to mediate the expression of antimicrobial peptides, induction of autophagy, as well as the production of reactive oxygen species and reactive nitrogen species as mechanisms of host defense. The role of vitamin D has been well characterized in the context of tuberculosis from both a molecular and epidemiological standpoint. Activation of Toll-like receptors, a family of innate immune pattern recognition receptors, on human macrophages with Mycobacterium tuberculosis-derived ligands results in activation of the vitamin D pathway, including (1) the conversion of 25-hydroxyvitamin D (25(OH)D) to 1,25-dihydroxyvitamin D (1,25(OH)2 D), (2) activation of the VDR, and (3) antimicrobial activity against intracellular M. tuberculosis infection. This provides a potential explanation for the association between the host vitamin D status with susceptibility to tuberculosis infection and disease.