Use of Vitamin A Supplementation to Enhance Neutrophil Function

Abstract

Vitamin A is a micronutrient essential for growth, cellular differentiation, reproduction, vision, and immunity. Retinoic acid (RA), the active metabolite of Vitamin A, affects transcriptional activity by binding to its receptors, RARs (Retinoic Acid Receptors) and RXRs (Retinoid X Receptors). Vitamin A is essential for immunity in humans, and deficiency is associated with increased morbidity and mortality from infectious diseases. Vitamin A deficient (VAD) neutrophils and macrophages exhibit impaired phagocytosis and bacterial killing, and infectious diseases can cause VAD by decreasing intake, decreasing absorption, and increasing excretion of Vitamin A. Thus, VAD and infection are thought to exist in a “vicious cycle”.Here, we investigated whether RA treatment enhances neutrophil killing and has direct antibacterial activity. Human neutrophils were pretreated with RA and then tested for their ability to kill E. coli K1, S. aureus MRSA, and S. pyogenes. We found that RA induced production of both reactive oxygen species (ROS) and neutrophil extracellular traps (NETs), critical mediators of neutrophil bactericidal activity, and enhanced killing of all bacteria tested. RA was also found to have direct activity against S. pyogenes. These results suggest a potential for RA as a treatment for bacterial infections.This work was supported by the UNCF‐Merck Science Initiative Postdoctoral Fellowship (EA), and NIH grants AI096837 and AI077780 (VN).