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.

Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis

“…In vivo studies showed that vitamin D suppressed intracellular growth of M. tuberculosis (22). Cathelicidin expression, which is the first line of defense in patients, is induced by vitamin D (23).…”

Antimicrobial implications of vitamin D

“…8 Vitamin D may also improve survival in acute illness by boosting innate immunity. 9 Vitamin D appears to have systemic antimicrobial effects 10 that may be crucial in a variety of both acute and chronic illness. The current use of antimicrobials in the United States costs billions of dollars.…”

“…109 Although eating refined carbohydrates and poor dental hygiene contribute to dental caries, vitamin D can reduce the risk of caries by inducing production of cathelicidin and defensins, which have antibacterial properties. 10 A cross-sectional study from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States found a significant inverse correlation between periodontal disease (PD) and serum 25(OH)D concentrations. 110 A study of British Bangladeshi adults, free of known diabetes or major illness, showed that a year of modest vitamin D supplementation decreased serum circulating MMP-9 levels by 69%.…”

An estimate of the global reduction in mortality rates through doubling vitamin D levels

“…In the United States, those with darker skin have increased risk (Sharip et al, 2006), and rates are highest in winter and lowest in summer (Kinlin et al, 2009;Sharip et al, 2006). Because meningitis is linked to bacterial infections, and vitamin D reduces the risk of bacterial infections through induction of cathelicidin and defensins (Gombart, 2009), one can reasonably expect vitamin D to reduce the risk of meningitis.…”