Neisseria meningitidis elicits a pro-inflammatory response involving IM-NM-:BM-NM-6 in a human blood-cerebrospinal fluid barrier model.

ABSTRACT: The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis world-wide. It has been described that Nm can enter the central nervous system via the blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus. Using a recently established in vitro model of the human BCSFB based on human malignant choroid plexus papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain MC58. In comparison we analysed the answer to the closely related unencapsulated carrier isolate Nm M-NM-114. Transcriptome analysis revealed 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 NF-M-NM-:B-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IM-NM-:BM-NM-6. Consistent with this, infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, among others, IL8, CXCL1-3 and the IM-NM-:BM-NM-6 target gene product IL6. Expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2 rather than TLR4 is involved in the cellular reaction following Nm infection. Human malignant choroid plexus papilloma (HIBCPP) cells were infected from the basolateral side with the meningitis-causing Neisseria meningitidis disease isolate MC58, its non-capsulated mutant MC58siaD- and the Neisseria meningitidis carrier isolate M-NM-114 for 4 h.The transcriptional response of HIBCPP cells to the different Neisseria meningitidis strains was evaluated by microarray analysis. Untreated HIBCPP cells served as control. Three replicates of each condition were analysed.

ORGANISM(S): Homo sapiens

SUBMITTER: Carsten Sticht 

PROVIDER: E-GEOD-42870 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress