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On the induction of inflammatory reactions by Streptococcus pyogenes

Påhlman, Lisa LU (2007)
Abstract
Streptococcus pyogenes is an important human pathogen that causes significant morbidity and mortality worldwide. In order to successfully infect the human host, S. pyogenes is equipped with tools that modulate the human immune defence. The present thesis explores how different streptococcal proteins interfere with innate immunity, adaptive immunity, and blood coagulation.



M protein is a surface-bound streptococcal virulence factor with antiphagocytic properties. M proteins can be released from the bacterial surface, and in the present thesis we report that soluble M1 protein is a potent activator of monocytes and T cells. M1 protein-induced monocyte activation involves Toll-like receptor (TLR) 2, and results in secretion... (More)
Streptococcus pyogenes is an important human pathogen that causes significant morbidity and mortality worldwide. In order to successfully infect the human host, S. pyogenes is equipped with tools that modulate the human immune defence. The present thesis explores how different streptococcal proteins interfere with innate immunity, adaptive immunity, and blood coagulation.



M protein is a surface-bound streptococcal virulence factor with antiphagocytic properties. M proteins can be released from the bacterial surface, and in the present thesis we report that soluble M1 protein is a potent activator of monocytes and T cells. M1 protein-induced monocyte activation involves Toll-like receptor (TLR) 2, and results in secretion of the pro-inflammatory cytokines IL-6, IL-1? and TNF?. In addition, monocytes treated with M1 protein up-regulate Tissue Factor (TF) expression on the cell surface, leading to activation of the extrinsic pathway of coagulation. T cell induction upon M1 protein stimulation results in a potent Th1 type response. Activation does not require normal antigen processing, it is MHC class II dependent, and V? restricted with preferential expansion of V?2 and 4 bearing T cells, suggesting that M1 protein functions as a superantigen.



Thrombin activatable fibrinolysis inhibitor (TAFI) is a human procarboxypeptidase circulating in plasma. When activated, TAFI inhibits fibrinolysis and modulates the immune system by cleaving inflammatory mediators such as C5a, fibrinopeptides and bradykinin. Here we find that TAFI binds to Streptococcal collagen-like surface protein A and B on S. pyogenes. These bacteria can also recruit the two TAFI activators thrombin and plasmin to the bacterial surface, leading to the activation of surface-bound TAFI.



Taken together, the findings may help explain how S. pyogenes modulates the immune response in order to successfully infect its human host. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Dr Talay, Susanne, Department of Microbial Pathogenesis, Helmholtz-Centre for Infection Research (HZI), Braunschweig, G
organization
publishing date
type
Thesis
publication status
published
subject
keywords
mycology, Mikrobiologi, bakteriologi, virologi, mykologi, virology, bacteriology, Microbiology, Streptococcal collagen-like surface protein, M protein, Inflammation, Streptococcus pyogenes
pages
151 pages
publisher
Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund
defense location
Segerfalksalen, Biomedicinskt Centrum, Sölvegatan 19, Lund
defense date
2007-02-23 09:15
ISSN
1652-8220
ISBN
978-91-85559-23-7
language
English
LU publication?
yes
id
1ac266d4-5a38-473b-a4e3-55e8121fac2e (old id 548051)
date added to LUP
2007-09-12 09:41:05
date last changed
2016-09-19 08:44:56
@phdthesis{1ac266d4-5a38-473b-a4e3-55e8121fac2e,
  abstract     = {Streptococcus pyogenes is an important human pathogen that causes significant morbidity and mortality worldwide. In order to successfully infect the human host, S. pyogenes is equipped with tools that modulate the human immune defence. The present thesis explores how different streptococcal proteins interfere with innate immunity, adaptive immunity, and blood coagulation.<br/><br>
<br/><br>
M protein is a surface-bound streptococcal virulence factor with antiphagocytic properties. M proteins can be released from the bacterial surface, and in the present thesis we report that soluble M1 protein is a potent activator of monocytes and T cells. M1 protein-induced monocyte activation involves Toll-like receptor (TLR) 2, and results in secretion of the pro-inflammatory cytokines IL-6, IL-1? and TNF?. In addition, monocytes treated with M1 protein up-regulate Tissue Factor (TF) expression on the cell surface, leading to activation of the extrinsic pathway of coagulation. T cell induction upon M1 protein stimulation results in a potent Th1 type response. Activation does not require normal antigen processing, it is MHC class II dependent, and V? restricted with preferential expansion of V?2 and 4 bearing T cells, suggesting that M1 protein functions as a superantigen.<br/><br>
<br/><br>
Thrombin activatable fibrinolysis inhibitor (TAFI) is a human procarboxypeptidase circulating in plasma. When activated, TAFI inhibits fibrinolysis and modulates the immune system by cleaving inflammatory mediators such as C5a, fibrinopeptides and bradykinin. Here we find that TAFI binds to Streptococcal collagen-like surface protein A and B on S. pyogenes. These bacteria can also recruit the two TAFI activators thrombin and plasmin to the bacterial surface, leading to the activation of surface-bound TAFI.<br/><br>
<br/><br>
Taken together, the findings may help explain how S. pyogenes modulates the immune response in order to successfully infect its human host.},
  author       = {Påhlman, Lisa},
  isbn         = {978-91-85559-23-7},
  issn         = {1652-8220},
  keyword      = {mycology,Mikrobiologi,bakteriologi,virologi,mykologi,virology,bacteriology,Microbiology,Streptococcal collagen-like surface protein,M protein,Inflammation,Streptococcus pyogenes},
  language     = {eng},
  pages        = {151},
  publisher    = {Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund},
  school       = {Lund University},
  title        = {On the induction of inflammatory reactions by Streptococcus pyogenes},
  year         = {2007},
}