Vitamin D- Immunmodulator der bakteriellen Meningitis

Vitamin D- Immunmodulator der bakteriellen Meningitis

Vitamin D- Immunmodulator of the bacterial meningitis

Marie Luise Onken

Doctoral thesis

Date of Examination: 2020-12-31

Date of issue: 2020-09-10

Advisor: Djukic, Marija Prof.Dr.

Referee: Weber, Martin Prof. Dr.

Referee: Oppermann, Martin Prof. Dr.

Persistent Address: http://hdl.handle.net/21.11130/00-1735-0000-0005-1480-3

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Abstract

English

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 microglia cultures after stimulation with the Toll-like receptors (TLR) agonists tripalmitoyl-S-glyceryl-cysteine (TLR1/2), Polynosine-polycytidylic acid (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 (IL)-6 was decreased in vitamin D-deficient compared to vitamin D-sufficient microglial cultures. Phagocytosis of E. coli K1 after stimulation of microglial cells with high concentrations of TLR 3, - 4 and 9 agonists and intracellular killing of E. coli K1 after stimulation with high concentrations of all TLR agonists was lower in vitamin D-deficient microglial than in the respective control cells. Our observations suggest that vitamin D deficiency may impair the resistance of the brain against bacterial infections.

Keywords: bacterial meningitis; vitamin D