25(OH)D(3) affects the maturation and function of mouse bone marrow-derived dendritic cells stimulated by Mycobacterium bovis BCG.

Abstract

It has been shown that vitamin D deficiency increases an individual's susceptibility to tuberculosis (TB). However, very little is known about the effect of vitamin D on the immune response to Mycobacterium tuberculosis (M. tb) in dendritic cells (DCs). Because DCs play an important role in TB infection, we investigated the phenotypic characteristics and functional capabilities of mouse bone marrow-derived dendritic cells (BMDCs) after stimulation with Bacillus Calmette-Guérin (BCG) in the presence or absence of 25(OH)D(3)(100 nM). Bone marrow cells from mice were cultured with GM-CSF (20 ng/ml) and were then treated with 25(OH)D(3) for 7 days. On day 6, 5 µg/ml of BCG (≥1.0×10(6) CFU/mg) was added to the cells for 24 hours, and on day 7, the non-adherent cells were harvested for phenotypic and functional analyses. After incubation with 25(OH)D(3), the expression levels of MHC-II and CD86 on the surface of the dendritic cells (DCs) and the ability of the DCs to stimulate proliferation of allogeneic mixed lymphocytes were lower than control cells (p<0.05). Furthermore, the level of Interleukin (IL) -4 secreted by the BMDCs in the 25(OH)D(3) culture was lower than that in the control culture (p<0.01). However, the BMDCs cultured with 25(OH)D(3) produced significantly higher levels of IL-2, IL-6, IL-10 and interferon gamma(IFN-γ) than those in the control culture (p<0.05). These findings suggest that 25(OH)D(3) modulates the immune response during mycobacterial infection by affecting the maturation and function of DCs.