Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis

Abstract Background The Gram-negative bacterium Neisseria meningitidis (Nm) can cause meningitis in humans, but the host signalling pathways manipulated by Nm during central nervous system (CNS) entry are not completely understood. Methods We investigate the role of the mitogen-activated protein kin...

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Autores principales:	Rosanna Herold, René Scholtysik, Selina Moroniak, Christel Weiss, Hiroshi Ishikawa, Horst Schroten, Christian Schwerk
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Blood-cerebrospinal fluid barrier Host innate signalling Host pathogen interaction MAPK Meningitis Neisseria meningitidis Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/2fb56ec244bc48a29398730361f8c302
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spelling	oai:doaj.org-article:2fb56ec244bc48a29398730361f8c3022021-12-05T12:04:33ZCapsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis10.1186/s12987-021-00288-72045-8118https://doaj.org/article/2fb56ec244bc48a29398730361f8c3022021-12-01T00:00:00Zhttps://doi.org/10.1186/s12987-021-00288-7https://doaj.org/toc/2045-8118Abstract Background The Gram-negative bacterium Neisseria meningitidis (Nm) can cause meningitis in humans, but the host signalling pathways manipulated by Nm during central nervous system (CNS) entry are not completely understood. Methods We investigate the role of the mitogen-activated protein kinases (MAPK) Erk1/2 and p38 in an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with Nm serogroup B (NmB) and serogroup C (NmC) strains. A transcriptome analysis of HIBCPP cells following infection with Nm by massive analysis of cDNA ends (MACE) was done to further characterize the cellular response to infection of the barrier. Results Interestingly, whereas NmB and NmC wild type strains required active Erk1/2 and p38 pathways for infection, invasion by capsule-deficient mutants was independent of Erk1/2 and, in case of the NmB strain, of p38 activity. The transcriptome analysis of HIBCPP cells following infection with Nm demonstrated specific regulation of genes involved in the immune response dependent on Erk1/2 signalling. Gene ontology (GO) analysis confirmed loss of MAPK signalling after Erk1/2 inhibition and revealed an additional reduction of cellular responses including NFκB and JAK-STAT signalling. Interestingly, GO terms related to TNF signalling and production of IL6 were lost specifically following Erk1/2 inhibition during infection with wild type Nm, which correlated with the reduced infection rates by the wild type in absence of Erk1/2 signalling. Conclusion Our data point towards a role of MAPK signalling during infection of the CP epithelium by Nm, which is strongly influenced by capsule expression, and affects infection rates as well as the host cell response.Rosanna HeroldRené ScholtysikSelina MoroniakChristel WeissHiroshi IshikawaHorst SchrotenChristian SchwerkBMCarticleBlood-cerebrospinal fluid barrierHost innate signallingHost pathogen interactionMAPKMeningitisNeisseria meningitidisNeurology. Diseases of the nervous systemRC346-429ENFluids and Barriers of the CNS, Vol 18, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Blood-cerebrospinal fluid barrier Host innate signalling Host pathogen interaction MAPK Meningitis Neisseria meningitidis Neurology. Diseases of the nervous system RC346-429
spellingShingle	Blood-cerebrospinal fluid barrier Host innate signalling Host pathogen interaction MAPK Meningitis Neisseria meningitidis Neurology. Diseases of the nervous system RC346-429 Rosanna Herold René Scholtysik Selina Moroniak Christel Weiss Hiroshi Ishikawa Horst Schroten Christian Schwerk Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
description	Abstract Background The Gram-negative bacterium Neisseria meningitidis (Nm) can cause meningitis in humans, but the host signalling pathways manipulated by Nm during central nervous system (CNS) entry are not completely understood. Methods We investigate the role of the mitogen-activated protein kinases (MAPK) Erk1/2 and p38 in an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with Nm serogroup B (NmB) and serogroup C (NmC) strains. A transcriptome analysis of HIBCPP cells following infection with Nm by massive analysis of cDNA ends (MACE) was done to further characterize the cellular response to infection of the barrier. Results Interestingly, whereas NmB and NmC wild type strains required active Erk1/2 and p38 pathways for infection, invasion by capsule-deficient mutants was independent of Erk1/2 and, in case of the NmB strain, of p38 activity. The transcriptome analysis of HIBCPP cells following infection with Nm demonstrated specific regulation of genes involved in the immune response dependent on Erk1/2 signalling. Gene ontology (GO) analysis confirmed loss of MAPK signalling after Erk1/2 inhibition and revealed an additional reduction of cellular responses including NFκB and JAK-STAT signalling. Interestingly, GO terms related to TNF signalling and production of IL6 were lost specifically following Erk1/2 inhibition during infection with wild type Nm, which correlated with the reduced infection rates by the wild type in absence of Erk1/2 signalling. Conclusion Our data point towards a role of MAPK signalling during infection of the CP epithelium by Nm, which is strongly influenced by capsule expression, and affects infection rates as well as the host cell response.
format	article
author	Rosanna Herold René Scholtysik Selina Moroniak Christel Weiss Hiroshi Ishikawa Horst Schroten Christian Schwerk
author_facet	Rosanna Herold René Scholtysik Selina Moroniak Christel Weiss Hiroshi Ishikawa Horst Schroten Christian Schwerk
author_sort	Rosanna Herold
title	Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
title_short	Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
title_full	Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
title_fullStr	Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
title_full_unstemmed	Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
title_sort	capsule-dependent impact of mapk signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by neisseria meningitidis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2fb56ec244bc48a29398730361f8c302
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Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis

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