Infection with Prevotella nigrescens induces TLR2 signalling and low levels of p65 mediated inflammation in Cystic Fibrosis bronchial epithelial cells

Anne Bertelsen, Joseph Elborn, Bettina Schock

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2 Citations (Scopus)
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Abstract

Prevotella spp. are frequently identified in Cystic Fibrosis sputum. This study examined whether infection with Prevotella nigrescens, a frequently identified member of this species, contributes to inflammation in CF bronchial epithelial cells through activation of TLR- and NF-κB signalling pathways. CFBE41o- cells were infected with either P.nigrescens or Pseudomonas aeruginosa and incubated under anaerobic conditions for 4 hours. P.nigrescens activated TLR2 signalling but not TLR4 signalling while P.aeruginosa activated TLR4 signalling with a lesser effect on TLR2.

P.aeruginosa induced significant IκBα phosphorylation 10 minutes post infection with a return to control levels by 30 minutes post infection. A significant induction in nuclear p65 DNA binding was observed at 2 hours post infection. In contrast, infection with P.nigrescens induced phosphorylation of IκBα 120 minutes post infection, with significant induction in nuclear p65 DNA binding at 4 hours post infection only. Cytokine gene and protein responses were lower for P.nigrescens compared to P.aeruginosa.

This study demonstrates the ability of a clinical P.nigrescens isolate to provoke a delayed NF-κB(p65) driven response through induction in TLR2 signalling and activation of sustained levels of IKKα.
Original languageEnglish
JournalJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Early online date10 Oct 2019
DOIs
Publication statusEarly online date - 10 Oct 2019

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