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Activation of TAFI on the Surface of Streptococcus pyogenes Evokes Inflammatory Reactions by Modulating the Kallikrein/Kinin System

Bengtson, Sara LU ; Sandén, Caroline LU ; Mörgelin, Matthias LU ; Marx, Pauline LU ; Olin, Anders LU ; Leeb-Lundberg, Fredrik LU ; Meijers, Joost C. M. and Herwald, Heiko LU (2009) In Journal of Innate Immunity 1(1). p.18-28
Abstract
Bacteria-controlled regulation of host responses to infection is an important virulence mechanism that has been demonstrated to contribute to disease progression. Here we report that the human pathogen Streptococcus pyogenes employs the procarboxypeptidase TAR (thrombin-activatablefibrinolysis inhibitor) to modulate the kallikrein/kinin system. To this end, bacteria initiate a chain of events starting with the recruitment and activation of TAFI. This is followed by the assembly and induction of the contact system at the streptococcal surface, eventually triggering the release of bradykinin (BK). BK is then carboxyterminally truncated by activated TAFI, which converts the peptide from a kinin B-2 receptor ligand to a kinin B-1 receptor... (More)
Bacteria-controlled regulation of host responses to infection is an important virulence mechanism that has been demonstrated to contribute to disease progression. Here we report that the human pathogen Streptococcus pyogenes employs the procarboxypeptidase TAR (thrombin-activatablefibrinolysis inhibitor) to modulate the kallikrein/kinin system. To this end, bacteria initiate a chain of events starting with the recruitment and activation of TAFI. This is followed by the assembly and induction of the contact system at the streptococcal surface, eventually triggering the release of bradykinin (BK). BK is then carboxyterminally truncated by activated TAFI, which converts the peptide from a kinin B-2 receptor ligand to a kinin B-1 receptor (B1R) agonist. Finally, we show that streptococcal supernatants indirectly amplify the B1R response as they act on peripheral blood mononuclear cells to secrete inflammatory cytokines that in turn stimulate upregulation of the B1R on human fibroblasts. Taken together our findings implicate a critical and novel role for streptococci-bound TAR, as it processes BK to a B1R agonist at the bacterial surface and thereby may redirect inflammation from a transient to a chronic state. Copyright (C) 2008 S. Karger AG, Basel (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Vascular biology, Thrombosis, Proteolysis, Hemostasis, Phagocytes
in
Journal of Innate Immunity
volume
1
issue
1
pages
18 - 28
publisher
Karger
external identifiers
  • wos:000268024800003
  • scopus:62249101697
ISSN
1662-811X
DOI
10.1159/000145543
language
English
LU publication?
yes
id
601fe702-1003-4d4d-a0cb-d54f0c71c0a7 (old id 1462522)
date added to LUP
2009-08-31 10:39:50
date last changed
2017-09-10 03:41:08
@article{601fe702-1003-4d4d-a0cb-d54f0c71c0a7,
  abstract     = {Bacteria-controlled regulation of host responses to infection is an important virulence mechanism that has been demonstrated to contribute to disease progression. Here we report that the human pathogen Streptococcus pyogenes employs the procarboxypeptidase TAR (thrombin-activatablefibrinolysis inhibitor) to modulate the kallikrein/kinin system. To this end, bacteria initiate a chain of events starting with the recruitment and activation of TAFI. This is followed by the assembly and induction of the contact system at the streptococcal surface, eventually triggering the release of bradykinin (BK). BK is then carboxyterminally truncated by activated TAFI, which converts the peptide from a kinin B-2 receptor ligand to a kinin B-1 receptor (B1R) agonist. Finally, we show that streptococcal supernatants indirectly amplify the B1R response as they act on peripheral blood mononuclear cells to secrete inflammatory cytokines that in turn stimulate upregulation of the B1R on human fibroblasts. Taken together our findings implicate a critical and novel role for streptococci-bound TAR, as it processes BK to a B1R agonist at the bacterial surface and thereby may redirect inflammation from a transient to a chronic state. Copyright (C) 2008 S. Karger AG, Basel},
  author       = {Bengtson, Sara and Sandén, Caroline and Mörgelin, Matthias and Marx, Pauline and Olin, Anders and Leeb-Lundberg, Fredrik and Meijers, Joost C. M. and Herwald, Heiko},
  issn         = {1662-811X},
  keyword      = {Vascular biology,Thrombosis,Proteolysis,Hemostasis,Phagocytes},
  language     = {eng},
  number       = {1},
  pages        = {18--28},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Activation of TAFI on the Surface of Streptococcus pyogenes Evokes Inflammatory Reactions by Modulating the Kallikrein/Kinin System},
  url          = {http://dx.doi.org/10.1159/000145543},
  volume       = {1},
  year         = {2009},
}