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

Laura Julia Starost, Sascha Karassek, Yasuteru Sano, Takashi Kanda, Kwang Sik Kim, Ulrich Dobrindt, Christian Rüter, Marcus Alexander Schmidt

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number291
JournalToxins
Volume8
Issue number10
DOIs
StatePublished - Oct 2016

Keywords

  • Blood–brain barrier
  • MAPK p38
  • NF-κB
  • NMEC
  • Neonatal meningitis-causing E. coli K1-RS218
  • Pertussis toxin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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