Vitamin D
Many reviews discuss the role of vitamin D and its metabolites in host immunity and susceptibility to infections [99–101].
Vitamin D receptors have been identified in most immune cells, of which some can also synthesize the active form of vitamin D from its precursor, therefore suggesting that might have important immunoregulatory properties [99]. Vitamin D is synthesized at skin level in the presence of UV-light from cholesterol and it is also taken up from the diet (fish, eggs, fortified milk, and mushrooms). The active form of vitamin D, calcitriol (1,25-dihydroxy vitamin D3), formed following kidney and liver hydroxylation, is most renowned for its regulating role in calcium homeostasis and bone health status, but it has also been shown to regulate the immune system, mainly in the functioning of T-cell [102].
Among the main functions of vitamin D, its ability to improve the integrity of the epithelium has mainly been observed as well as the ability to induce the synthesis of an antimicrobial peptide in epithelial cells and macrophages, thus directly improving host defense [103]. Vitamin D also promotes the differentiation of monocytes from macrophages [95], promotes the movement and phagocyability of macrophages [79], superoxide production and bacterial killing by innate immune cells. Hence, it promotes the processing of antigen presentation by dendritic cells [104].
Calcitriol regulates the expression of antimicrobial proteins (cathelicidin and defensin), which directly kill pathogens, especially bacteria [99]. It inhibits the production of IFN-γ [71] and reduces the expression of pro-inflammatory cytokines by increasing the expression of anti-inflammatory cytokines by macrophages [105]. Calcitriol modulates antimicrobial proteins (cathelicidin and β-defensin), responsible for modifying the intestinal microbiota, favoring a healthy composition and supporting the intestinal barrier [80, 106]. It also helps protect the lungs against infection, increases the expression of the tight junction protein, E-cadherin and connexion 43 in the intestine, maintains renal-epithelial barrier function and improves corneal epithelial barrier function [104].
The 1,25-dihydroxyvitamin D3 can bind to a specific nuclear receptor (vitamin D receptor, VDR) and its role for both the innate and adaptive immune systems has been highlighted [107].
Moreover, vitamin D has been controversially discussed for its role in influenza prevention and therapy. As shown in literature, 1,25-dihydroxyvitamin D3 undoubtedly plays a strong role as an immunomodulating agent in adaptive and innate immunity. Different reviews have also reported that individuals with low vitamin D status have a higher risk of viral respiratory tract infections [99, 108].
Several systematic reviews show that levels of this vitamin are inversely related to respiratory tract infection [109, 110] and underlines that individuals with low vitamin D levels show an increased risk of viral tract infections, concluding that its supplementation can reduce the risk of respiratory tract infections [82, 111].
Some studies on the influenza prevention provide a negative correlation between the enhanced post-immunization vaccine and obese patients, because obesity involves a deficiency of vitamin D. According to most authors, more randomized controlled trials with large populations are needed to explore the preventive effect of vitamin D supplementation on viral flu infections [107].