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Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory – Jan 2021

JBMR® Vol. 5, No. 1, January 2021, DOI: 10.1002/jbm4.10405
Emma L Bishop" Aiten Ismailova,2t Sarah Dimeloe,1,3 Martin Hewison,3© and John H White2,4
1 institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
2Department of Physiology, McGill University, Montreal, Quebec, Canada
3Metabolism and Systems Research, University of Birmingham, Birmingham, UK
4Department of Medicine, McGill University, Montreal, Quebec, Canada
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Table of contents

  • Vitamin D Metabolism in the Innate Immune System
  • 1,25D Induces Antimicrobial Innate Immunity
  • 1,25D Regulates Pattern Recognition Receptor Gene Expression
  • 1,25D Regulates Expression of Cytokines Important in Innate Immunity
  • Vitamin D and Granulocyte Biology
  • Effects of Vitamin D on NK, NKT, and y5 T Cells
  • Vitamin D and T Cells
  • Direct Effects of 1,25D on T Cells
  • Effects of 1,25D on T-Cell Metabolism
  • Indirect Effects of Vitamin D on T Cells
  • Anti-Inflammatory Effects of Vitamin D and Autoimmune Disease
  • Vitamin D and Antiviral Innate Immunity
  • Vitamin D and COVID-19
  • Conclusions

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Virus category listing has 737 items along with related searches

Overview Influenza and vitamin D
Search for treg OR "t-cell" in VitaminDWiki 1440 items as of Jan 2020
141 VitaminDWiki pages contained "infection" in title (June 2021)
Search VitaminDWik for BACTERIA in title 25 items as of Aug 2019
Vitamin D and the Immune System – chapter Aug 2019
7X less risk of influenza if Vitamin D levels higher than 30 ng – Oct 2017
Common cold prevented and treated by Vitamin D, Vitamin C, Zinc, and Echinacea – review April 2018
Vitamin D improves T Cell immunity – RCT Feb 2016
Immune system - great 11-minute animated video - Aug 2021 nothing about Vitamin D
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Regulation of immune function continues to be one of the most well-recognized extraskeletal actions of vitamin D. This stemmed initially from the discovery that antigen presenting cells such as macrophages could actively metabolize precursor 25-hydroxyvitamin D (25D) to active 1,25-dihydroxyvitamin D (1,25D). Parallel observation that activated cells from the immune system expressed the intracellular vitamin D receptor (VDR) for 1,25D suggested a potential role for vitamin D as a localized endogenous modulator of immune function. Subsequent studies have expanded our understanding of how vitamin D exerts effects on both the innate and adaptive arms of the immune system. At an innate level, intracrine synthesis of 1,25D by macrophages and dendritic cells stimulates expression of antimicrobial proteins such as cathelicidin, as well as lowering intracellular iron concentrations via suppression of hepcidin. By potently enhancing autophagy, 1,25D may also play an important role in combatting intracellular pathogens such as M. tuberculosis and viral infections. Local synthesis of 1,25D by macrophages and dendritic cells also appears to playa pivotal role in mediating T-cell responses to vitamin D, leading to suppression of inflammatory T helper (Th)1 and Th17 cells, and concomitant induction of immunotolerogenic T- regulatory responses. The aim of this review is to provide an update on our current understanding of these prominent immune actions of vitamin D, as well as highlighting new, less well-recognized immune effects of vitamin D. The review also aims to place this mechanistic basis for the link between vitamin D and immunity with studies in vivo that have explored a role for vitamin D supplementation as a strategy for improved immune health. This has gained prominence in recent months with the global coronavirus disease 2019 health crisis and highlights important new objectives for future studies of vitamin D and immune function.

Conclusions

There is strong evidence that vitamin D metabolic enzymes are expressed in virtually all cells in the innate and adaptive arms of the immune system. Considering the findings discussed above, vitamin D signaling appears to influence susceptibility to and severity of bacterial and viral infection via several mechanisms. These include its direct effects on the production of antimicrobial peptides and cytokines, as well as its regulation of the NF-kB pathway during infection. Overall, preclinical and clinical data propose a strong link between vitamin D status and susceptibility to infectious and autoimmune diseases. There is evidence that vitamin D deficiency during early life may predispose the immune system to a greater risk of autoimmune disease or allergy.(345) Several laboratory and clinical studies have provided support for a role of vitamin D in combating respiratory tract infections. Evaluation of vitamin D supplementation as an adjuvant therapeutic intervention could be clinically and economically significant in the ongoing COVID-19 crisis, as well as in the treatment of other infectious diseases. Based on the immunoreg- ulatory properties of vitamin D presented above, improving circulating 25D levels may slow progression of disease or even ameliorate patient survival. Though the evidence fora mechanistic role for vitamin D signaling in immune system regulation is highly compelling, there is still a need for large-scale randomized controlled trials to confirm whether maintaining vitamin D sufficiency reduces the incidence and severity of infections and/or autoimmune diseases.


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