Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

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.

Abstract

Neutrophil elastase cleaves thrombin generating anti-inflammatory peptides. Here the authors show that cleavage of thrombin by Pseudomonas aeruginosa elastase generates a peptide that prevents TLR dimerization and signaling, interfering with the inflammatory response to avoid host defense.