Figure 1.

Schematic representation of the primary mechanisms through which vitamin D regulates macrophage-mediated innate immune response.

Notes: vitamin D from sunlight or dietary sources is hydroxylated by the 25-hydroxylase to form its major circulating form – 25(OH)D₃. 25(OH)D₃ is then hydroxylated by 1α-hydroxylase (CYP27B1) to form the hormonal form of vitamin D – 1,25(OH)₂D₃. 1,25(OH)₂D₃ acts to modulate TLR signaling via stimulating SOCS1, inhibiting the phosphorylation of p38 MAPK and activation of NF-κB signaling in human macrophages, which reduces the gene expression and protein release of proinflammatory mediators, such as TNFα, IL-6, and MCP-1, leading to decreased recruitment of monocytes/macrophages and overall inflammation within tissue. In addition, 1,25(OH)₂D₃ acts to increase the production of the antimicrobial peptide cathelicidin and the killing of intracellular mycobacterium tuberculosis (MTB).

Abbreviations: LPS, lipopolysaccharide; VDR, vitamin D receptor; VDREs, vitamin D response elements; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein-1; TLR, toll-like receptor; TNFα, tumor necrosis factor-α.