The Vitamin D–antimicrobial Peptide Pathway and Its Role in Protection against Infection

Adrian F Gombart

Disclosures

Future Microbiol. 2009;4(9):1151-1165. 

In This Article

Abstract and Introduction

Abstract

Vitamin D deficiency has been correlated with increased rates of infection. Since the early 19th century, both environmental (i.e., sunlight) and dietary sources (cod liver) of vitamin D have been identified as treatments for TB. The recent discovery that vitamin D induces antimicrobial peptide gene expression explains, in part, the 'antibiotic' effect of vitamin D and has greatly renewed interest in the ability of vitamin D to improve immune function. Subsequent work indicates that this regulation is biologically important for the response of the innate immune system to wounds and infection and that deficiency may lead to suboptimal responses toward bacterial and viral infections. The regulation of the cathelicidin antimicrobial peptide gene is a human/primate-specific adaptation and is not conserved in other mammals. The capacity of the vitamin D receptor to act as a high-affinity receptor for vitamin D and a low-affinity receptor for secondary bile acids and potentially other novel nutritional compounds suggests that the evolutionary selection to place the cathelicidin gene under control of the vitamin D receptor allows for its regulation under both endocrine and xenobiotic response systems. Future studies in both humans and humanized mouse models will elucidate the importance of this regulation and lead to the development of potential therapeutic applications.

Introduction

Vitamin D insufficiency/deficiency is a worldwide, public health problem in both developed and developing countries. Vitamin D promotes and maintains healthy bones and teeth, but with the near eradication of rickets in the early part of the 20th century by fortification of foods, chronic insufficiency has gone largely unrecognized. However, with the current reemergence of nutritional rickets among infants, recent evidence that low levels of circulating vitamin D are associated with increased risk and mortality from cancer, and evidence of the beneficial effects of vitamin D on multiple sclerosis, rheumatoid arthritis, diabetes, cardiovascular disease and microbial infections, there has been renewed interest in this vitamin. In 2007, Time magazine cited the "benefits of vitamin D" in its list of "Top 10 Medical Breakthroughs". Although extensive research has been done on vitamin D, the molecular and cellular mechanisms responsible for its many benefits have not been fully elucidated. With the discovery that vitamin D regulates the expression of an important antimicrobial peptide gene, exciting research findings are revealing and characterizing new pathways regulated by vitamin D and its receptor that may be essential for optimal immune function.

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