Vitamin d deficiency reduces the immune response, phagocytosis rate, and intracellular killing rate of microglial cells

• Published in: Infection and immunity 2014-06, Vol.82 (6), p.2585-2594
• Main Authors: Djukic, Marija, Onken, Marie Luise, Schütze, Sandra, Redlich, Sandra, Götz, Alexander, Hanisch, Uwe-Karsten, Bertsch, Thomas, Ribes, Sandra, Hanenberg, Andrea, Schneider, Simon, Bollheimer, Cornelius, Sieber, Cornel, Nau, Roland
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Bacterial Infections; Calcifediol - blood; Cell Survival; Cells, Cultured; Chemokines - metabolism; Colony Count, Microbial; Cytokines - metabolism; Disease Models, Animal; Escherichia coli; Escherichia coli - physiology; Immunity, Innate - physiology; Lipopolysaccharides - pharmacology; Meningitis, Escherichia coli - immunology; Meningitis, Escherichia coli - physiopathology; Mice; Mice, Inbred C57BL; Microglia - drug effects; Microglia - microbiology; Microglia - physiology; Nitric Oxide - metabolism; Phagocytosis - physiology; Toll-Like Receptors - agonists; Vitamin D - physiology; Vitamin D Deficiency - immunology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.01814-14

Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality and neurological sequelae. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D. Vitamin D has potent effects on human immunity, including induction of antimicrobial peptides (AMPs) and suppression of T-cell proliferation, but its influence on microglial cells is unknown. The purpose of the present study was to determine the effects of vitamin D deficiency on the phagocytosis rate, intracellular killing, and immune response of murine microglial cultures after stimulation with the Toll-like receptor (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), poly(I·C) (TLR3), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9). Upon stimulation with high concentrations of TLR agonists, the release of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) was decreased in vitamin D-deficient compared to that in vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR3, -4, and -9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists were lower in vitamin D-deficient microglial cells than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections.