Mucoid Pseudomonas aeruginosa caused by mucA mutations result in activation of TLR2 in addition to TLR5 in airway epithelial cells.
The presence of the mucoid phenotype of Pseudomonas aeruginosa is a marker of poor survival in cystic fibrosis. As CF lung disease results from chronic infection leading to airway inflammation, we determined whether the switch to a mucoid phenotype by P. aeruginosa has an impact on the inflammatory response of airway epithelial cells. Exposure of airway epithelial cells to non-mucoid and mucoid P. aeruginosa-derived material leads to p38α MAPK activation, a key protein kinase involved in transmitting inflammatory signals. However, while the non-mucoid strain PAO1 activates p38α MAPK pathway solely via TLR5, the mucoid strain PACF508 activates p38α MAPK via both TLR5 and TLR2. Inactivation of mucA (the gene responsible for the mucoid phenotype) in PAO1 leads to p38α MAPK activation by both TLR2 and TLR5, as observed in the clinical mucoid isolate PACF508. Therefore, the switch to mucoid phenotype may contribute to more inflammation via TLR2 activation in addition to TLR5. Our findings highlight an important and under recognized role for TLR2 in the response of airway epithelial cells to infection.
Meakins-Christie Laboratories, McGill University, Montreal, Canada.
Trevor
T
Beaudoin
Shantelle
S
Lafayette
Dao
D
Nguyen
Simon
S
Rousseau
D001426:Bacterial Proteins / Q000235:genetics*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D051198:Toll-Like Receptor 5 / Q000819:agonists*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis
D001426:Bacterial Proteins; C107895:MucA protein, Pseudomonas; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051198:Toll-Like Receptor 5; D048051:p38 Mitogen-Activated Protein Kinases