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Open AccessArticle

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion

1
Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
2
Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
3
Central Facility for Microscopy, Helmholtz Centre for Infection Research, Inhoffenstraße 7, D-38124 Braunschweig, Germany
4
Laboratory of Clinical Regenerative Medicine, Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, 1-1-1Tennodai, Tsukuba, Ibaraki 305-8575, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(16), 5739; https://doi.org/10.3390/ijms21165739
Received: 26 June 2020 / Revised: 5 August 2020 / Accepted: 6 August 2020 / Published: 10 August 2020
(This article belongs to the Special Issue Choroid Plexus: Novel Functions for an Old Structure)
Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood–brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood–cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis. View Full-Text
Keywords: choroid plexus; blood–cerebrospinal fluid barrier; NTHI; Haemophilus influenzae; host pathogen interaction; meningitis choroid plexus; blood–cerebrospinal fluid barrier; NTHI; Haemophilus influenzae; host pathogen interaction; meningitis
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Wegele, C.; Stump-Guthier, C.; Moroniak, S.; Weiss, C.; Rohde, M.; Ishikawa, H.; Schroten, H.; Schwerk, C.; Karremann, M.; Borkowski, J. Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion. Int. J. Mol. Sci. 2020, 21, 5739.

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