Abstract
Biofilm microcolonies of Pseudomonas aeruginosa chronically infect the airways of patients with cystic fibrosis and fuel ongoing destructive inflammation, yet the impact of the switch from planktonic to biofilm growth on host responses is poorly understood. We report that in airway epithelial cells a threshold of p38α mitogen-activated protein kinase (MAPK) activation was required to trigger neutrophil recruitment, which is influenced by extrinsic and intrinsic factors. Planktonic P. aeruginosa diffusible material (PsaDM) induced stronger p38α MAPK activation as compared to biofilm PsaDM. Biofilm PsaDM activated p38α MAPK in a Toll-like receptor-independent fashion via the lasI/lasR quorum-sensing system, but this activation was insufficient to recruit neutrophils. However, in airway epithelial cells from patients with cystic fibrosis with hypersensitivity to injurious stimuli, biofilm PsaDM activated p38α MAPK strongly enough to recruit neutrophils, which can contribute to lung injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Biofilms / growth & development*
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Biopsy
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Cells, Cultured
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Cystic Fibrosis / immunology
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Cystic Fibrosis / microbiology
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Enzyme-Linked Immunosorbent Assay
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Epithelial Cells / immunology*
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Epithelial Cells / microbiology
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Humans
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Immunity, Innate*
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Immunoblotting
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Mitogen-Activated Protein Kinase 14 / immunology*
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Mitogen-Activated Protein Kinase 14 / metabolism
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NF-kappa B / metabolism
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Nasal Mucosa / cytology
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Neutrophil Infiltration
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Neutrophils / metabolism
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Neutrophils / microbiology
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Plankton / metabolism
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Pseudomonas aeruginosa / immunology*
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Pseudomonas aeruginosa / pathogenicity*
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Quorum Sensing
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Respiratory System / cytology
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Respiratory System / enzymology
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Respiratory System / immunology
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Respiratory System / microbiology
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / genetics
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Trans-Activators / metabolism
Substances
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Bacterial Proteins
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LasI protein, Pseudomonas aeruginosa
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LasR protein, Pseudomonas aeruginosa
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NF-kappa B
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Trans-Activators
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Mitogen-Activated Protein Kinase 14