Nutrients. 2016 Dec; 8(12): 806.
Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

Edwin Hoe,1 Jordan Nathanielsz,1 Zheng Quan Toh,1 Leena Spry,1 Rachel Marimla,1 Anne Balloch,1 Kim Mulholland,1,2 and Paul V. Licciardi1,3,*
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1Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne VIC 3052, Australia; ua.ude.ircm@eoh.niwde (E.H.); ua.ude.ircm@zsleinahtan.nadroj (J.N.); ua.ude.ircm@hotnauq.gnehz (Z.Q.T.); ua.ude.ircm@yrps.aneel (L.S.); ua.ude.ircm@almiram.lehcar (R.M.); ua.ude.ircm@hcollab.enna (A.B.); (K.M.)
2London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
3Department of Paediatrics, The University of Melbourne, Parkville VIC 3010, Australia

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.

维生素D具有多种免疫调节功能。维生素D受体(VDR)广泛表达于所有免疫细胞亚群,通过维生素D连接VDR可激活关键的先天免疫细胞,如单核细胞、巨噬细胞和中性粒细胞,从而增强趋化、吞噬和杀菌活性[11,12,13]。VDR结合1,25(OH)2D3的亲和力远远大于25(OH)D3[14]。维生素D也调节toll样受体的表达(通常)[15]和受体CD14[16]在重要的先天免疫细胞,促进25 (OH) D3的转换活动形式(dihydroxyvitamin D3-1, 25 (OH) 2 D3),并诱发生产抗菌肽、抗菌肽等抑制革兰氏阳性和革兰氏阴性细菌的生长(17、18)。维生素D还通过上调IL-10[19]来促进抗炎作用。因此,维生素D可能在调节细菌特异性炎症反应中起关键作用。

Keywords: vitamin D, inflammation, bacterial infection, pneumococcal

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection