Microbial interaction: Prevotella spp. reduce P. aeruginosa induced inflammation in Cystic Fibrosis bronchial epithelial cells

Anne Bertelsen, J. Stuart Elborn, Bettina C. Schock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In Cystic Fibrosis (CF) airways, the dehydrated, thick mucus promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, the vicious, selfperpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa ( P. aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known.
Materials: We assessed innate immune signalling in CF airway epithelial cells in
response to clinical strains of P. histicola, P. nigresens and P. aeruginosa. CFBE41ocells were infected with P. aeruginosa (MOI 100, 2h) followed by infection with P. histicola or P. nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments.
Results: Our study shows that P. histicola and P. nigresens can reduce the growth
of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of the investigated Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-kB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections.
Conclusion: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobic Prevotella spp.. The observed modified NF-kB and MAPK signalling indicates some mechanisms underlying this interaction that could offer a novel therapeutic approach to combat chronic P. aeruginosa infection in people with CF.
Original languageEnglish
Number of pages10
JournalJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
Early online date08 Jun 2021
DOIs
Publication statusEarly online date - 08 Jun 2021

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