Activation of TAFI on the Surface of Streptococcus pyogenes Evokes Inflammatory Reactions by Modulating the Kallikrein/Kinin System
Author
Summary, in English
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
Department/s
- Infection Medicine (BMC)
- Drug Target Discovery
Publishing year
2009
Language
English
Pages
18-28
Publication/Series
Journal of Innate Immunity
Volume
1
Issue
1
Document type
Journal article
Publisher
Karger
Topic
- Immunology in the medical area
Keywords
- Vascular biology
- Thrombosis
- Proteolysis
- Hemostasis
- Phagocytes
Status
Published
Research group
- Drug Target Discovery
ISBN/ISSN/Other
- ISSN: 1662-811X