Abstract
Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived peptide FYT21, which inhibits pro-inflammatory responses to several pathogen-associated molecular patterns in vitro and in vivo by preventing toll-like receptor dimerization and subsequent activation of down-stream signalling pathways. Thus, P. aeruginosa 'hijacks' an endogenous anti-inflammatory peptide-based mechanism, thereby enabling modulation and circumvention of host responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / metabolism*
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Cell Membrane / metabolism
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Cytokines / metabolism
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Host-Pathogen Interactions*
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Humans
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Inflammation / pathology*
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Leukocytes / metabolism
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Leukocytes / ultrastructure
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Lipopolysaccharides / metabolism
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Metalloendopeptidases / metabolism*
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Mice
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Microbial Viability
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NF-kappa B / metabolism
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Peptides / isolation & purification
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Peptides / metabolism*
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Protein Binding
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Thrombin / metabolism*
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Toll-Like Receptor 4 / agonists
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Toll-Like Receptor 4 / metabolism
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Transcription Factor AP-1 / metabolism
Substances
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Bacterial Proteins
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Cytokines
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Lipopolysaccharides
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NF-kappa B
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Peptides
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Toll-Like Receptor 4
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Transcription Factor AP-1
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Thrombin
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Metalloendopeptidases
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pseudolysin, Pseudomonas aeruginosa