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Open Access 01-12-2014 | Research

Neisseria meningitidiselicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model

Authors: Julia Borkowski, Li Li, Ulrike Steinmann, Natascha Quednau, Carolin Stump-Guthier, Christel Weiss, Peter Findeisen, Norbert Gretz, Hiroshi Ishikawa, Tobias Tenenbaum, Horst Schroten, Christian Schwerk

Published in: Journal of Neuroinflammation | Issue 1/2014

Abstract

Background

The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis worldwide. The blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus (CP), has been suggested as one of the potential entry sites of Nm into the CSF and can contribute to the inflammatory response during infectious diseases of the brain. Toll-like receptors (TLRs) are involved in mediating signal transduction caused by the pathogens.

Methods

Using a recently established in vitro model of the human BCSFB based on human malignant CP papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain, MC58, employing transcriptome and RT-PCR analysis, cytokine bead array, and enzyme-linked immunosorbent assay (ELISA). In comparison, we analyzed the answer to the closely related unencapsulated carrier isolate Nm α14. The presence of TLRs in HIBCPP and their role during signal transduction caused by Nm was studied by RT-PCR and the use of specific agonists and mutant bacteria.

Results

We observed a stronger transcriptional response after infection with strain MC58, in particular with its capsule-deficient mutant MC58siaD^-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NFκB-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IκBζ. Infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, including, among others, IL8, CXCL1-3, and the IκBζ target gene product IL6. The expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2/TLR6, rather than TLR4 or TLR2/TLR1, is involved in the cellular reaction following Nm infection.

Conclusions

Our data show that Nm can initiate a pro-inflammatory response in human CP epithelial cells probably involving TLR2/TLR6 signaling and the transcriptional regulator IκBζ.

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Title: Neisseria meningitidiselicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model
Authors: Julia Borkowski
Li Li
Ulrike Steinmann
Natascha Quednau
Carolin Stump-Guthier
Christel Weiss
Peter Findeisen
Norbert Gretz
Hiroshi Ishikawa
Tobias Tenenbaum
Horst Schroten
Christian Schwerk
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2014
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/s12974-014-0163-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Neisseria meningitidiselicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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