Vitamin D dependent anti-microbial pathways
Vitamin D is a pluripotent secosteroid whose actions extend far beyond classical effects on calcium homeostasis and bone metabolism. Vitamin D is known to exert powerful effects on both innate and adaptive immunity, with important consequences for both infectious and autoimmune diseases. Innate immune activities of vitamin D include the attenuation of antigen presentation by dendritic cells. However, recent attention has focused on the ability of vitamin D to stimulate antibacterial responses, notably in monocytes and macrophages, involving localized induction of the enzyme responsible for synthesis of active, 1,25-dihydroxyvitamin D (1,25D), namely CYP27B1, and the nuclear vitamin D receptor (VDR). The mechanism for this involves pathogen-sensing by toll-like receptors (TLRs) but may also be influenced by other tissue-specific factors such as growth factors. Enhanced expression of CYP27B1 and VDR facilitates intracrine conversion of the main serum form of vitamin D, 25-hydroxyvitamin D (25D) to 1,25D. The resulting rise in cellular 1,25D is then able to promote VDR-mediated transcriptional activity. In particular, locally synthesized 1,25D has been shown to induce antibacterial proteins such as cathelicidin which are central to the killing of bacteria and mycobacteria. As a result of these observations it appears that vitamin D may be a key factor in infectious diseases such as tuberculosis. The efficacy of vitamin D in promoting innate immune responses is dependent on several factors including the expression and induction of TLRs. However, the most important consideration appears to be the availability of 25D for intracrine conversion to 1,25D. Given that 25D reflects the vitamin D status of individuals, it has been proposed that vitamin D-insufficiency may compromise innate immunity and predispose to infectious disease. These issues will be discussed in the symposium with specific reference to the mechanisms involved in mediating the interaction between vitamin D and the immune system.