A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes
Oehmcke, Sonja ; Westman, Johannes LU ; Malmström, Johan LU
; Mörgelin, Matthias
LU
; Olin, Anders
LU
; Kreikemeyer, Bernd
and Herwald, Heiko
LU
(2013)
In PLoS Pathogens
9(8).
- Abstract
- 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,... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4062510
- author
- Oehmcke, Sonja
; Westman, Johannes
LU
; Malmström, Johan
LU
; Mörgelin, Matthias
LU
; Olin, Anders
LU
; Kreikemeyer, Bernd
and Herwald, Heiko
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 9
- issue
- 8
- article number
- e1003529
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000323888200030
- scopus:84883417355
- ISSN
- 1553-7366
- DOI
- 10.1371/journal.ppat.1003529
- project
- Contact system project
- language
- English
- LU publication?
- yes
- id
- 3cde6d64-e689-4ff5-b283-003f965b4083 (old id 4062510)
- date added to LUP
- 2016-04-01 10:04:15
- date last changed
- 2022-01-25 19:23:13
@article{3cde6d64-e689-4ff5-b283-003f965b4083,
abstract = {{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.}},
author = {{Oehmcke, Sonja and Westman, Johannes and Malmström, Johan and Mörgelin, Matthias and Olin, Anders and Kreikemeyer, Bernd and Herwald, Heiko}},
issn = {{1553-7366}},
language = {{eng}},
number = {{8}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS Pathogens}},
title = {{A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes}},
url = {{https://lup.lub.lu.se/search/files/1531681/4354992.pdf}},
doi = {{10.1371/journal.ppat.1003529}},
volume = {{9}},
year = {{2013}},
}