Vitamin D, infections and immunity

Abstract

Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.

Relationship between Vitamin D Status and Antibody Response to COVID-19 mRNA Vaccination in Healthy Adults

“…In addition to the immune system, protective effects of vitamin D are also described on ACE2 expression and the renin-angiotensin system (RAS) [ 10 ]. The experimental findings are supported by a number of successful clinical studies, which overall contribute to the high regard for vitamin D as a promising supplement in prevention and a meaningful adjuvant in the treatment of COVID-19 [ 11 , 12 ]. Therefore, active supplementation is considered and strongly recommended by leading experts around the world [ 5 , 13 , 14 , 15 ].…”

The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2

“…Vitamin D (Vit D) is an oxysterol hormone with important immunomodulatory and antiviral properties [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Even though this vitamin is often recommended as a nutritional supplement in treatment guidelines and prescribed for the management of coronavirus disease 2019 (COVID-19) [ 9 , 10 , 11 , 12 ], several studies have yielded divergent or inconclusive results [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Gut microbiome, Vitamin D, ACE2 interactions are critical factors in immune-senescence and inflammaging: key for vaccine response and severity of COVID-19 infection

“…Vit D deficiency leads to an upregulation of RAS/ACE signaling and pro-inflammatory activity. This may enhance the severity in COVID-19 sepsis with clinical features of ARDS, pulmonary edema, cardiovascular injury and thrombotic events [77,87].…”