title: Staphylococcus aureus Inhibits IL-8 Responses Induced by Pseudomonas aeruginosa in Airway Epithelial Cells.
abstract: Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are major respiratory pathogens and can concurrently colonize the airways of patients with chronic obstructive diseases, such as cystic fibrosis (CF). Airway epithelial cell signalling is critical to the activation of innate immune responses. In the setting of polymicrobial colonization or infection of the respiratory tract, how epithelial cells integrate different bacterial stimuli remains unknown. Our study examined the inflammatory responses to PA and SA co-stimulations. Immortalised airway epithelial cells (Beas-2B) exposed to bacteria-free filtrates from PA (PAF) induced a robust production of the neutrophil chemoattractant IL-8 while bacteria-free filtrates from SA (SAF) had a minimal effect. Surprisingly, co-stimulation with PAF+SAF demonstrated that SAF strongly inhibited the PAF-driven IL-8 production, showing that SAF has potent anti-inflammatory effects. Similarly SAF decreased IL-8 production induced by the TLR1/TLR2 ligand Pam3CysSK4 but not the TLR4 ligand LPS nor TLR5 ligand flagellin in Beas-2B cells. Moreover, SAF greatly dampened TLR1/TLR2-mediated activation of the NF-κB pathway, but not the p38 MAPK pathway. We observed this SAF-dependent anti-inflammatory activity in several SA clinical strains, as well as in the CF epithelial cell line CFBE41o-. These findings show a novel direct anti-inflammatory effect of SA on airway epithelial cells, highlighting its potential to modulate inflammatory responses in the setting of polymicrobial infections.
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Chekabab
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Silverman
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Shantelle L
authors.initials: SL
authors.lastname: Lafayette
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Rousseau
authors.affiliation: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Dao
authors.initials: D
authors.lastname: Nguyen
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*; D051194:Toll-Like Receptor 1 / Q000819:agonists / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006460:Hemolysin Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D048051:p38 Mitogen-Activated Protein Kinases