Sequential transmigration of polymorphonuclear cells and naive CD3 +  T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30

Dahm, Tobias; Frank, Franziska; Adams, Ortwin; Lindner, Holger A.; Ishikawa, Hiroshi; Weiß, Christel; Schwerk, Christian; Schroten, Horst; Tenenbaum, Tobias; Rudolph, Henriette

doi:10.1016/j.virusres.2017.01.024

Cited by 12 publications

(17 citation statements)

References 123 publications

(147 reference statements)

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“…Preliminary observations made with the Th cell subsets used in the present study confirm involvement of GPCR signaling in the diapedesis of all Th subsets across BLEC monolayers. Furthermore, our previous studies have shown that addition of exogenous CXCL12 to the CSF side increased T-cell migration across HIBCPP monolayers [31,68,69]. These data support the additional role for GPCR signaling in the migration of effector Th cell subsets across the BBB and BCSFB.…”

Section: Discussionsupporting

confidence: 74%

Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

Nishihara

Soldati

Mossu

et al. 2020

Fluids Barriers CNS

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Background: The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial bloodcerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). Objective: Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4 + T-cell subsets across the BBB versus the BCSFB. Methods: Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4 + T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro. Results: While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10-to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barriercrossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. Conclusions: Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.

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Section: Discussionsupporting

confidence: 74%

Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

Nishihara

Soldati

Mossu

et al. 2020

Fluids Barriers CNS

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“…Infection with EV30 results in the upregulation of the chemokines CXCL-3, -10, -11, -20 as well as IL-8 and macrophage colony-stimulating factor (M-CSF). During EV30 infection, there is predominantly a polar direction of cytokine/chemokine secretion in the basolateral side of the CP, with only IL-7 being secreted on the apical side to the CSF [162].…”

Section: Viral Infectionsmentioning

confidence: 99%

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Solar

Zamani

Kubíčková

et al. 2020

Fluids Barriers CNS

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The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…For assessment of PMN and T-cell transmigration across the HIBCPP cell layer, an infection experiment over 24 h with an MOI of 0.7 was carried out. As recently described, PMN and naïve CD3 + T-cells were isolated from human blood of healthy donors [ 23 ]. Each cell population was labelled either with CellTrace™ Calcein red-orange or with CellTrace™ Calcein green (Molecular probes, USA) according to manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…The effect of different NPEVs on the barrier function and morphology of the BCSFB has not been investigated yet. Previously, it could be demonstrated that E-30 Bastianni can infect human choroid plexus epithelial (HIBCPP) cells and lead to alteration of barrier function [ 19 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this context, NPEV meningitis is often accompanied by CSF pleocytosis with an early influx of polymorphonuclear (PMN) cells [ 24 – 27 ] followed by increasing numbers of CD4 + T-cells [ 28 ]. For the BCSFB, it was recently shown that E-30 infection resulted in an enhanced migration of PMN and T-cells in vitro [ 23 ]. Leukocyte migration across endothelium or epithelium can occur via two routes, para- and transcellular [ 29 – 34 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier

Dahm

Adams

Boettcher

et al. 2018

J Neuroinflammation

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BackgroundEchovirus (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.MethodsWe 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.ResultsWe 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.ConclusionThe 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.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1061-4) contains supplementary material, which is available to authorized users.

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Sequential transmigration of polymorphonuclear cells and naive CD3 + T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30

Cited by 12 publications

References 123 publications

Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

Human CD4+ T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro

Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Strain-dependent effects of clinical echovirus 30 outbreak isolates at the blood-CSF barrier

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