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

TY - JOUR

T1 - Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

AU - van der Plas, Mariena J A

AU - Bhongir, Ravi K V

AU - Kjellström, Sven

AU - Siller, Helena

AU - Kasetty, Gopinath

AU - Mörgelin, Matthias

AU - Schmidtchen, Artur

PY - 2016/5/16

Y1 - 2016/5/16

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/ncomms11567

DO - 10.1038/ncomms11567

M3 - Journal article

C2 - 27181065

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11567

ER -