Staphylococcus aureus Inhibits IL-8 Responses Induced by Pseudomonas aeruginosa in Airway Epithelial Cells
Samuel M Chekabab1, Richard J Silverman2, Shantelle L Lafayette1
1Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; Meakins Christie Laboratories, McGill University, Montreal, Quebec, Canada.
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.
Insights
Staphylococcus aureus (SA) can suppress Pseudomonas aeruginosa (PA)-induced inflammation in airway cells. This finding reveals a novel anti-inflammatory role for SA in polymicrobial respiratory infections, impacting conditions like cystic fibrosis.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are key respiratory pathogens often co-infecting patients with chronic obstructive diseases, like cystic fibrosis (CF).
- Airway epithelial cells are crucial for innate immune responses, but how they integrate signals from multiple bacteria during co-infection is unclear.
Purpose of the Study:
- To investigate the inflammatory responses of airway epithelial cells to co-stimulation with PA and SA.
- To determine if SA modulates the inflammatory effects of PA in airway epithelial cells.
Main Methods:
- Immortalised human airway epithelial cells (Beas-2B) and a CF epithelial cell line (CFBE41o-) were stimulated with bacteria-free filtrates from PA (PAF) and SA (SAF).
- Inflammatory cytokine (IL-8) production and signalling pathways (NF-κB, p38 MAPK) were analyzed.
- Responses to TLR ligands (Pam3CysSK4, LPS, flagellin) were assessed.
Main Results:
- PAF induced significant IL-8 production, while SAF had minimal effect.
- Co-stimulation with SAF strongly inhibited PAF-induced IL-8 production, demonstrating an anti-inflammatory effect of SA.
- SAF specifically inhibited IL-8 production induced by the TLR1/TLR2 ligand Pam3CysSK4 and dampened TLR1/TLR2-mediated NF-κB activation, but not responses to LPS or flagellin.
Conclusions:
- Staphylococcus aureus possesses a direct, potent anti-inflammatory effect on airway epithelial cells.
- This anti-inflammatory activity of SA can modulate host responses during polymicrobial respiratory infections.
- SA's ability to suppress inflammation warrants further investigation in the context of diseases like cystic fibrosis.
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