A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

Research output: Contribution to journalArticle

Standard

A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes. / Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders; Kreikemeyer, Bernd; Herwald, Heiko.

In: PLoS Pathogens, Vol. 9, No. 8, e1003529, 2013.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Oehmcke, Sonja ; Westman, Johannes ; Malmström, Johan ; Mörgelin, Matthias ; Olin, Anders ; Kreikemeyer, Bernd ; Herwald, Heiko. / A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes. In: PLoS Pathogens. 2013 ; Vol. 9, No. 8.

RIS

TY - JOUR

T1 - A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

AU - Oehmcke, Sonja

AU - Westman, Johannes

AU - Malmström, Johan

AU - Mörgelin, Matthias

AU - Olin, Anders

AU - Kreikemeyer, Bernd

AU - Herwald, Heiko

PY - 2013

Y1 - 2013

N2 - Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a K-D value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases.

AB - Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a K-D value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases.

U2 - 10.1371/journal.ppat.1003529

DO - 10.1371/journal.ppat.1003529

M3 - Article

VL - 9

JO - PLoS Pathogens

T2 - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1003529

ER -