A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes.
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...
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2013
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oai:doaj.org-article:a5357a4d02c94a959fb8eb244dbf27232021-11-18T06:07:49ZA novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes.1553-73661553-737410.1371/journal.ppat.1003529https://doaj.org/article/a5357a4d02c94a959fb8eb244dbf27232013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935504/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Previous 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 KD 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.Sonja OehmckeJohannes WestmanJohan MalmströmMatthias MörgelinAnders I OlinBernd KreikemeyerHeiko HerwaldPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 8, p e1003529 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sonja Oehmcke Johannes Westman Johan Malmström Matthias Mörgelin Anders I Olin Bernd Kreikemeyer Heiko Herwald A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| description |
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 KD 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. |
| format |
article |
| author |
Sonja Oehmcke Johannes Westman Johan Malmström Matthias Mörgelin Anders I Olin Bernd Kreikemeyer Heiko Herwald |
| author_facet |
Sonja Oehmcke Johannes Westman Johan Malmström Matthias Mörgelin Anders I Olin Bernd Kreikemeyer Heiko Herwald |
| author_sort |
Sonja Oehmcke |
| title |
A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| title_short |
A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| title_full |
A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| title_fullStr |
A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| title_full_unstemmed |
A novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| title_sort |
novel role for pro-coagulant microvesicles in the early host defense against streptococcus pyogenes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/a5357a4d02c94a959fb8eb244dbf2723 |
| work_keys_str_mv |
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