Vitamin D, innate immunity and upper respiratory tract infection

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Introduction

In 1903, the Danish doctor Niels Finsen was awarded the Nobel Prize for discovering that high intensity light produced from an electric arc lamp cured 95 per cent of patients with skin tuberculosis - a condition termed lupus vulgaris. By the 1920s, sun exposure was recognised as an effective treatment for pulmonary tuberculosis.¹ With the advent of penicillin and sulphanilamide, after the First World War, the idea that regular sun exposure might protect against infection was rapidly forgotten. However, over the last decade, research into the antimicrobial action of vitamin D has provided new insights into this historical intervention.² Recent laboratory^3-7 and epidemiological⁸ evidence suggests that vitamin D plays an important role in both adaptive and innate immunity. Local innate defences, which rapidly recognise potential microbial pathogens, play an important role in preventing microbial colonisation that could lead to recurrent infection.^9,10

This paper provides an overview of current knowledge on the contribution of vitamin D to innate immunity in the upper respiratory tract.

Mucosal defence and antimicrobial peptides

The upper respiratory tract is the primary site of contact for inhaled pathogens. Exposure to potential pathogens is common, and several protective mechanisms exist at mucosal surfaces. The first major physical defence covering the ciliated respiratory epithelium is a superficial gel layer of mucus which physically removes inhaled pathogens.^11,12 The second defence mechanisms are the antimicrobial peptides: defensins, cathelicidin, and larger antimicrobial proteins such as lysozyme, lactoferrin and secretory leukocyte protease inhibitor in the airway secretions.^13-15 The third defence mechanism is the initiation of the inflammatory response and the recruitment of phagocytic cells to any developing infection.¹²

Antimicrobial peptides, which are synthesised and released largely by epithelial cells and neutrophils, have a broad spectrum of antimicrobial activity against viruses, bacteria and fungi.^14,15 In contrast to many conventional antibiotics, these peptides appear to be bactericidal.¹⁵ Bacteria have difficulty developing resistance to antimicrobial peptides, although some bacteria have developed mechanisms to evade their action.² The initial contact between an antimicrobial peptide and the microbe is thought to be electrostatic, as antimicrobial peptides are positively charged and most bacterial surfaces are...