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Toxins 2016, 8(10), 291; doi:10.3390/toxins8100291

Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells

1
Institute of Infectiology, Center of Molecular Biology of Inflammation, Westfälische Wilhelms-Universität Münster, Münster D-48149, Germany
2
Department of Neurology and Clinical Neuroscience, Yamaguchi University Graduate School of Medicine, Yamaguchi, Ube City 755-8505, Japan
3
Pediatric Infectious Diseases Division, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
4
Institute of Hygiene, Microbial Genome Plasticity—Molecular Infection Biology, Westfälische Wilhelms-Universität Münster, Münster D-48149, Germany
These authors contributed equally to this study.
Present address: Oncology Business Unit, WuXi AppTec Inc., Shanghai 200131, China.
*
Author to whom correspondence should be addressed.
Academic Editor: Vernon Tesh
Received: 6 September 2016 / Revised: 30 September 2016 / Accepted: 1 October 2016 / Published: 13 October 2016
(This article belongs to the Section Bacterial Toxins)
View Full-Text   |   Download PDF [1636 KB, uploaded 13 October 2016]   |  

Abstract

Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. View Full-Text
Keywords: pertussis toxin; MAPK p38; neonatal meningitis-causing E. coli K1-RS218; NMEC; NF-κB; blood–brain barrier pertussis toxin; MAPK p38; neonatal meningitis-causing E. coli K1-RS218; NMEC; NF-κB; blood–brain barrier
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Starost, L.J.; Karassek, S.; Sano, Y.; Kanda, T.; Kim, K.S.; Dobrindt, U.; Rüter, C.; Schmidt, M.A. Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells. Toxins 2016, 8, 291.

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