Dataset Information

Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood-Cerebrospinal Fluid Barrier.

ABSTRACT: Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood-cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant decrease in the transepithelial electrical resistance of HIBCPP cells. However, to reach the same impact on the barrier properties, the multiplicity of infection of the apical side had to be higher than that of the basolateral infection. Furthermore, the number of infected cells at respective time-points after basolateral infection was significantly higher compared to apical infection. Cytotoxic effects of E-30 on HIBCPP cells during basolateral infection were observed following prolonged infection and appeared more drastically compared to the apical infection. Gene expression profiles determined by massive analysis of cDNA ends revealed distinct regulation of specific genes depending on the side of HIBCPP cells' infection. Altogether, our data highlights the polar effects of E-30 infection in a human in vitro model of the blood-cerebrospinal fluid barrier leading to central nervous system inflammation.

SUBMITTER: Wiatr M

PROVIDER: S-EPMC7503638 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood-Cerebrospinal Fluid Barrier.

Wiatr Marie M Figueiredo Ricardo R Stump-Guthier Carolin C Winter Peter P Ishikawa Hiroshi H Adams Ortwin O Schwerk Christian C Schroten Horst H Rudolph Henriette H Tenenbaum Tobias T

International journal of molecular sciences 20200829 17

Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood-cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant ...[more]

PMID: 32872518

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Project description:BACKGROUND:Echovirus (E) 30 (E-30) meningitis is characterized by neuroinflammation involving immune cell pleocytosis at the protective barriers of the central nervous system (CNS). In this context, infection of the blood-cerebrospinal fluid barrier (BCSFB), which has been demonstrated to be involved in enteroviral CNS pathogenesis, may affect the tight junction (TJ) and adherens junction (AJ) function and morphology. METHODS:We used an in vitro human choroid plexus epithelial (HIBCPP) cell model to investigate the effect of three clinical outbreak strains (13-311, 13-759, and 14-397) isolated in Germany in 2013, and compared them to E-30 Bastianni. Conducting transepithelial electrical resistance (TEER), paracellular dextran flux measurement, quantitative real-time polymerase chain reaction (qPCR), western blot, and immunofluorescence analysis, we investigated TJ and AJ function and morphology as well as strain-specific E-30 infection patterns. Additionally, transmission electron and focused ion beam microscopy electron microscopy (FIB-SEM) was used to evaluate the mode of leukocyte transmigration. Genome sequencing and phylogenetic analyses were performed to discriminate potential genetic differences among the outbreak strains. RESULTS:We observed a significant strain-dependent decrease in TEER with strains E-30 Bastianni and 13-311, whereas paracellular dextran flux was only affected by E-30 Bastianni. Despite strong similarities among the outbreak strains in replication characteristics and particle distribution, strain 13-311 was the only outbreak isolate revealing comparable disruptive effects on TJ (Zonula Occludens (ZO) 1 and occludin) and AJ (E-cadherin) morphology to E-30 Bastianni. Notwithstanding significant junctional alterations upon E-30 infection, we observed both para- and transcellular leukocyte migration across HIBCPP cells. Complete genome sequencing revealed differences between the strains analyzed, but no explicit correlation with the observed strain-dependent effects on HIBCPP cells was possible. CONCLUSION:The findings revealed distinct E-30 strain-specific effects on barrier integrity and junctional morphology. Despite E-30-induced barrier alterations leukocyte trafficking did not exclusively occur via the paracellular route.

Project description:BackgroundHypertension is an important risk factor for cerebrovascular disease, including stroke and dementia. Both in humans and animal models of hypertension, neuropathological features such as brain atrophy and oedema have been reported. We hypothesised that cerebrovascular damage resulting from chronic hypertension would manifest itself in a more permeable blood-brain barrier and blood-cerebrospinal fluid barrier. In addition, more leaky barriers could potentially contribute to an enhanced interstitial fluid and cerebrospinal fluid formation, which could, in turn, lead to an elevated intracranial pressure.MethodsTo study this, we monitored intracranial pressure and estimated the cerebrospinal fluid production rate in spontaneously hypertensive (SHR) and normotensive rats (Wistar Kyoto, WKY) at 10 months of age. Blood-brain barrier and blood-cerebrospinal fluid barrier integrity was determined by measuring the leakage of fluorescein from the circulation into the brain and cerebrospinal fluid compartment. Prior to sacrifice, a fluorescently labelled lectin was injected into the bloodstream to visualise the vasculature and subsequently study a number of specific vascular characteristics in six different brain regions.ResultsBlood and brain fluorescein levels were not different between the two strains. However, cerebrospinal fluid fluorescein levels were significantly lower in SHR. This could not be explained by a difference in cerebrospinal fluid turnover, as cerebrospinal fluid production rates were similar in SHR and WKY, but may relate to a larger ventricular volume in the hypertensive strain. Also, intracranial pressure was not different between SHR and WKY. Morphometric analysis of capillary volume fraction, number of branches, capillary diameter, and total length did not reveal differences between SHR and WKY.ConclusionIn conclusion, we found no evidence for blood-brain barrier or blood-cerebrospinal fluid barrier leakage to a small solute, fluorescein, in rats with established hypertension.

Dataset Information

Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood-Cerebrospinal Fluid Barrier.

Publications

Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood-Cerebrospinal Fluid Barrier.

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