Vitamin D-mediated effects on airway innate immunity in vitro

Abstract

Introduction Vitamin D supplementation has been suggested to enhance immunity during respiratory infection season. We tested the effect of active vitamin D (calcitriol) supplementation on key airway innate immune mechanisms in vitro. Methods Primary human airway epithelial cells (hAECs) grown at the air liquid interface were supplemented with 10−7 M calcitriol for 24 hours (or a time course) and their antimicrobial airway surface liquid (ASL) was tested for pH, viscoscity, and antibacterial and antiviral properties. We also tested hAEC ciliary beat frequency (CBF). Next, we assessed alterations to hAEC gene expression using RNA sequencing, and based on results, we measured neutrophil migration across hAECs. Results Calcitriol supplementation enhanced ASL bacterial killing of Staphylococcus aureus (p = 0.02) but did not enhance its antiviral activity against 229E-CoV. It had no effect on ASL pH or viscosity at three timepoints. Lastly, it did not affect hAEC CBF or neutrophil migration, although there was a trend of enhanced migration in the presence of a neutrophil chemokine (p = 0.09). Supplementation significantly altered hAEC gene expression, primarily of AMP-related genes including CAMP and TREM1. Conclusion While vitamin D supplementation did not have effects on many airway innate immune mechanisms, it may provide a useful tool to resolve respiratory bacterial infections.

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

“…They suggested that calcitriol acts by modulating the vitamin D receptor pathway to increase the expression of cathelicidin. It has effects on several innate immune mechanisms in the airway (Stapleton et al 2022 ). The conflicting effects of calcitriol may be due to differences in vitamin D metabolism and the dose of calcitriol given to mice may have been too low to maintain adequate levels.…”

Interrelationships between tuberculosis and chronic obstructive pulmonary disease

“…Levels of vitamin D in infancy did not predict TB disease (hazard ratio = 0.8, 95% CI, 0.4–1.6); however, severe vitamin D deficiency (<30 nmol/l) was associated with TB infection in children 2 years or less of age (aOR=1.9, 95% CI, 1.2–3.2) [85 ▪▪ ]. Mechanistically, vitamin D upregulates the expression of antimicrobial peptides, such as cathelicidin, a protein expressed by leukocytes and epithelial cells that disrupts the integrity of the bacterial cell membrane; thus, vitamin D has been proposed as a possible intervention to prevent bacterial infection [86,87 ▪ ]. In a large clinical trial, 8851 Mongolian children, 96% of whom were vitamin D deficient, were randomized to receive weekly oral vitamin D supplementation or placebo, and tested for TB infection (QuantiFERON-TB Gold) after a 3-year period [88].…”