On the induction of inflammatory reactions by Streptococcus pyogenes

Research output: ThesisDoctoral Thesis (compilation)

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On the induction of inflammatory reactions by Streptococcus pyogenes. / Påhlman, Lisa.

Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund, 2007. 151 p.

Research output: ThesisDoctoral Thesis (compilation)

Harvard

APA

Påhlman, L. (2007). On the induction of inflammatory reactions by Streptococcus pyogenes. Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund.

CBE

Påhlman L. 2007. On the induction of inflammatory reactions by Streptococcus pyogenes. Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund. 151 p.

MLA

Påhlman, Lisa On the induction of inflammatory reactions by Streptococcus pyogenes Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund. 2007.

Vancouver

Påhlman L. On the induction of inflammatory reactions by Streptococcus pyogenes. Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund, 2007. 151 p.

Author

Påhlman, Lisa. / On the induction of inflammatory reactions by Streptococcus pyogenes. Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund, 2007. 151 p.

RIS

TY - THES

T1 - On the induction of inflammatory reactions by Streptococcus pyogenes

AU - Påhlman, Lisa

N1 - Defence details Date: 2007-02-23 Time: 09:15 Place: Segerfalksalen, Biomedicinskt Centrum, Sölvegatan 19, Lund External reviewer(s) Name: Talay, Susanne Title: Dr Affiliation: Department of Microbial Pathogenesis, Helmholtz-Centre for Infection Research (HZI), Braunschweig, G --- <div class="article_info">Lisa I Påhlman, Matthias Mörgelin, Jana Eckert, Linda Johansson, Wayne Russel, Kristian Riesbeck, Oliver Soehnlein, Lennart Lindbom, Anna Norrby-Teglund, Ralf R Schumann, Lars Björck and Heiko Herwald. <span class="article_issue_date">2006</span>. <span class="article_title">Streptococcal M protein – a multipotent and powerful inducer of inflammation.</span> <span class="journal_series_title">Journal of Immunology</span>, <span class="journal_volume">vol 177</span> <span class="journal_pages">pp 1221-1228</span>.</div> <div class="article_info">Lisa I Påhlman, Erik Malmström, Matthias Mörgelin and Heiko Herwald. <span class="article_issue_date"></span>. <span class="article_title">M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes.</span> (submitted)</div> <div class="article_info">Lisa I Påhlman, Jessica Darenberg, Anders I Olin, Malak Kotb, Heiko Herwald and Anna Norrby-Teglund. <span class="article_issue_date"></span>. <span class="article_title">Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation.</span> (manuscript)</div> <div class="article_info">Lisa I Påhlman, Pauline F Marx, Matthias Mörgelin, Slawomir Lukomski, Joost C M Meijers and Heiko Herwald. <span class="article_issue_date"></span>. <span class="article_title">Thrombin Activatable Fibrinolysis Inhibitor binds to Streptococcus pyogenes by interacting with collagen-like surface proteins A and B.</span> (submitted)</div>

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - mycology

KW - Mikrobiologi

KW - bakteriologi

KW - virologi

KW - mykologi

KW - virology

KW - bacteriology

KW - Microbiology

KW - Streptococcal collagen-like surface protein

KW - M protein

KW - Inflammation

KW - Streptococcus pyogenes

M3 - Doctoral Thesis (compilation)

SN - 978-91-85559-23-7

PB - Lund University, Faculty of Medicine, Institution for Clinical Sciences Lund

ER -