title: Differential Contribution of the Aryl-Hydrocarbon Receptor and Toll-Like Receptor Pathways to IL-8 Expression in Normal and Cystic Fibrosis Airway Epithelial Cells Exposed toPseudomonas aeruginosa.
abstract: Pseudomonas aeruginosaare gram-negative bacteria that frequently infect the lungs of cystic fibrosis (CF) patients. This bacterium is highly responsive to changes in its environment, resulting in the expression of a diverse array of genes that may contribute to the host inflammatory response.P. aeruginosais well-known to induce neutrophilic inflammation via the activation of Toll-Like Receptors (TLRs). Recently, it was shown that pyocyanin, a phenazine produced byP. aeruginosa, binds to the aryl hydrocarbon receptor (AhR), leading to neutrophilic inflammation as part of the host defense response. In this study, we have investigated the contribution of the TLR and AhR signaling pathways to the expression of the neutrophil chemoattractant IL-8 in response toP. aeruginosadiffusible material. Although both pathways are involved in IL-8 synthesis, the AhR played a greater role when planktonicP. aeruginosawas grown in a media favoring phenazine synthesis. However, whenP. aeruginosawas grown in a media that mimics the nutritional composition of CF sputa, both pathways contributed similarly to IL-8 synthesis. Finally, whenP. aeruginosawas grown as a biofilm, the TLR pathway did not contribute to biofilm-driven IL-8 synthesis and AhR was found to only partially contribute to IL-8 synthesis, suggesting the contribution of another unknown signaling pathway. Therefore, the interaction betweenP. aeruginosaand airway epithelial cells is very dynamic, and sensor engagement is variable according to the adaptation ofP. aeruginosato the CF lung environment.
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, McGill University Health Centre Research Institute Montreal, QC, Canada.
authors.forename: Lucie
authors.initials: L
authors.lastname: Roussel
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, McGill University Health Centre Research Institute Montreal, QC, Canada.
authors.forename: Shantelle
authors.initials: S
authors.lastname: LaFayette
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, McGill University Health Centre Research Institute Montreal, QC, Canada.
authors.forename: Dao
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, McGill University Health Centre Research Institute Montreal, QC, Canada.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
authors.affiliation: Meakins-Christie Laboratories, Department of Medicine, McGill University, McGill University Health Centre Research Institute Montreal, QC, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Rousseau
keywords: TLR2; TLR5; biofilm; cystic fibrosis; epithelium; infection; inflammation; innate immunity