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

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

In: Journal of Neuroinflammation, 11 (2014), Nr. 163. pp. 1-18. ISSN 1742-2094

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Download (1MB) | Lizenz: Creative Commons LizenzvertragNeisseria meningitidis elicits a pro-inflammatory response involving IκBζ in a human blood-cerebrospinal fluid barrier model by Borkowski, Julia ; Li, Li ; Steinmann, Ulrike ; Quednau, Natascha ; Stump-Guthier, Carolin ; Weiß, Christel ; Findeisen, Peter ; Gretz, Norbert ; Ishikawa, Hiroshi ; Tenenbaum, Tobias ; Schroten, Horst ; Schwerk, Christian underlies the terms of Creative Commons Attribution 3.0 Germany

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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.

Item Type: Article
Journal or Publication Title: Journal of Neuroinflammation
Volume: 11
Number: 163
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 01 Mar 2016 08:25
Date: 2014
ISSN: 1742-2094
Page Range: pp. 1-18
Faculties / Institutes: Medizinische Fakultät Mannheim > Zentrum für Medizinische Forschung
Medizinische Fakultät Mannheim > Kinderklinik
Medizinische Fakultät Mannheim > Institut für Klinische Chemie
Medizinische Fakultät Mannheim > Medizinische Statistik, Biomathematik und Informationsverarbeitung
Subjects: 610 Medical sciences Medicine
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