Abstract
Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.
Highlights
Global burden of disease data estimates that infections are responsible for ~3 million deaths of children under five years of age per year [1]
Unstained peripheral blood mononuclear cells (PBMCs) were used as a control and a minimum of 20,000 events were analysed per sample gated on live, single cell lymphocyte gate based on FFS and SSC, where the expression of the cell surface molecules were evaluated using MFI values using BD FACSDiva 8.0.1 software (Becton, Dickinson and Company, Franklin Lakes, NJ, USA)
The cytokine response in PBMCs pre‐treated with 1,25(OH)2D3 and stimulated with heat-killed pneumococcal serotype 19F (HK19F) is shown ininFigure significantreduction reduction in TNF-α
Summary
Global burden of disease data estimates that infections are responsible for ~3 million deaths of children under five years of age per year [1]. Bacterial infections comprise a significant proportion of this, with Gram-positive and Gram-negative bacteria such as Streptococcus pneumoniae, Escherichia coli, and Salmonella typhi the leading candidates [2]. Exposure to these organisms can be extremely high, especially in low-income country settings, leading to persistent activation of host inflammatory responses. Given the paucity of data in relation to the immunomodulatory effects and possible protection elicited by vitamin D, we hypothesized that the active form of vitamin D, 1,25(OH) D3 , modulates critical host responses important in host protection against Gram-positive and Gram-negative infection
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