The Vitamin D–Antimicrobial Peptide Pathway and its Role in Protection Against Infection

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.

Keywords:

• antimicrobial peptide
• bile acid
• cathelicidin
• infection
• innate immunity
• intestinal
• steroid-hormone receptor
• vitamin D
• vitamin D receptor
• xenobiotic

Acknowledgements

The author would like to thank members of the laboratory for their useful discussions and apologizes to those authors whose interesting data could not be included owing to space constraints.

Financial & competing interests disclosure

This work was supported by grant 5R01AI065604–04 to the author from the National Institute of Allergy and Infectious Diseases at the NIH. The author has received a patent covering the use of vitamin D and its analogs to induce the cathelicidin gene. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by grant 5R01AI065604–04 to the author from the National Institute of Allergy and Infectious Diseases at the NIH. The author has received a patent covering the use of vitamin D and its analogs to induce the cathelicidin gene. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.