Vitamin D deficiency decreases survival of bacterial meningoencephalitis in mice.

Marija Djukic,Stefan Nessler,L Cornelius Bollheimer,Marianne Mecke,Jakob Triebel,Cornel Sieber,Anja Manig,Roland Nau,Uwe-Karsten Hanisch,Thomas Bertsch,Nadine Sostmann

doi:10.1186/s12974-014-0208-1

Abstract

BackgroundMeningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. A high prevalence of neurological disorders has been observed in geriatric populations at risk of hypovitaminosis D.MethodsIn vivo, we studied the effects of vitamin D3 on survival and the host’s immune response in experimental bacterial meningoencephalitis in mice after intracerebral E. coli infection. To produce different systemic vitamin D3 concentrations, mice received a low, standard, or high dietary vitamin D3 supplementation. Bacterial titers in blood, spleen, and brain homogenates were determined. Leukocyte infiltration was assessed by histological scores, and tissue cytokine or chemokine concentrations were measured.ResultsMice fed a diet with low vitamin D3 concentration died earlier than control animals after intracerebral infection. Vitamin D deficiency did not inhibit leukocyte recruitment into the subarachnoid space and did not lead to an increased density of bacteria in blood, spleen, or brain homogenates. The release of proinflammatory interleukin (IL)-6 was decreased and the release of anti-inflammatory IL-10 was increased in mice fed a diet with high vitamin D3 supplementation.ConclusionOur observations suggest a detrimental role of vitamin D deficiency in bacterial central nervous system infections. Vitamin D may exert immune regulatory functions.

Highlights

Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults
Vitamin D3 deficiency led to higher mortality of E. coli meningoencephalitis After intracerebral infection with 4,000 colony-forming unit (CFU), 15 of 17 vitamin D-deficient mice (L-VitD), 10 of 21 mice fed a standard vitamin D3 concentration (S-VitD) diet, and 8 of 15 mice fed a high vitamin D3 concentration (H-VitD) diet died (P = 0.002 low vitamin D concentrations (L-VitD) versus H-VitD, P = 0.003 L-VitD versus S-VitD, log-rank test, Figure 1A)
Our experiments identified for the first time a detrimental in-vivo effect of vitamin D deficiency on survival in experimental E. coli meningoencephalitis

Summary

Introduction

Meningoencephalitis caused by Escherichia coli is associated with high rates of mortality and risk of neurological sequelae in newborns and infants and in older or immunocompromised adults. Escherichia coli is a Gram-negative bacillus causing local infections in the urinary tract, abdomen, and lungs Systemic spread of these infections is frequent, leading to sepsis and meningoencephalitis, and is associated with high rates of mortality and morbidity in newborn infants, and in immunocompromised or elderly persons despite advances in antimicrobial chemotherapy [1]. The ability of bacteria to achieve high bacterial concentrations in blood, increasing the probability of invasion of the CNS, is greater in immunocompromised individuals (for example, neonates) than in immunocompetent adults, explaining the differences in the occurrence of E. coli K1 meningoencephalitis [6,7,8]. In Europe, antimicrobial resistance in Gram-negative bacteria is spreading, in Djukic et al Journal of Neuroinflammation (2015) 12:208

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