title: Vitamin d deficiency reduces the immune response, phagocytosis rate, and intracellular killing rate of microglial cells.
abstract: 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.
authors.affiliation: Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende, Göttingen, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Djukic
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Onken
authors.forename: Sandra
authors.initials: S
authors.lastname: Schütze
authors.forename: Sandra
authors.initials: S
authors.lastname: Redlich
authors.forename: Alexander
authors.initials: A
authors.lastname: Götz
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertsch
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.forename: Andrea
authors.initials: A
authors.lastname: Hanenberg
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.forename: Cornelius
authors.initials: C
authors.lastname: Bollheimer
authors.forename: Cornel
authors.initials: C
authors.lastname: Sieber
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002112:Calcifediol / Q000097:blood; D002470:Cell Survival; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000502:physiology*; D007113:Immunity, Innate / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020814:Meningitis, Escherichia coli / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D051193:Toll-Like Receptors / Q000819:agonists; D014807:Vitamin D / Q000502:physiology*; D014808:Vitamin D Deficiency / Q000276:immunology
chemical_list: D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D014807:Vitamin D; D009569:Nitric Oxide; D002112:Calcifediol