Vitamin D in Early Childhood and the Effect on Immunity to Mycobacterium tuberculosis

Figure 1

Mechanism of vitamin-D-induced immunity to Mycobacterium tuberculosis (modified from [16]). Stimulation of monocyte Toll-like receptors (TLR1/2) by Mycobacterium tuberculosis (MTB) results in transcriptional induction of the vitamin D receptor (VDR) and 1𝛼-hydroxylase (CYP27B1). Circulating 25-hydroxyvitamin D (25[OH]D) enters the cell and is converted to 1,25-dihydroxyvitamin D (1,25[OH]2D) by the CYP27B1 enzyme. VDR-bound 1,25(OH)2D then induces expression of cathelicidin and 𝛽-defensin 2 (DEFB4). In addition 1,25(OH)2D induces autophagy and downregulating metalloproteinases (MMPs), all of which help in the formation of phagolysosomes and the killing of Mtb. 1,25(OH)2D also affects the adaptive immune system and leads to an upregulation of regulatory responses and a skewing towards a Th2 response. IFN𝛾 is thought to induce the expression of the CYP27B1 enzyme suggesting a feedback mechanism between the innate and adaptive response to vitamin D.