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Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects

Sepsis is a life-threatening complication of infection that is characterized by a dysregulated inflammatory state and disturbed hemostasis. Platelets are the main regulators of hemostasis, and they also respond to inflammation. The human pathogen Streptococcus pyogenes can cause local infection that...

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Autores principales: Palm, Frida, Chowdhury, Sounak, Wettemark, Sara, Malmström, Johan, Happonen, Lotta, Shannon, Oonagh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852700/
https://www.ncbi.nlm.nih.gov/pubmed/34898252
http://dx.doi.org/10.1128/iai.00462-21
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author Palm, Frida
Chowdhury, Sounak
Wettemark, Sara
Malmström, Johan
Happonen, Lotta
Shannon, Oonagh
author_facet Palm, Frida
Chowdhury, Sounak
Wettemark, Sara
Malmström, Johan
Happonen, Lotta
Shannon, Oonagh
author_sort Palm, Frida
collection PubMed
description Sepsis is a life-threatening complication of infection that is characterized by a dysregulated inflammatory state and disturbed hemostasis. Platelets are the main regulators of hemostasis, and they also respond to inflammation. The human pathogen Streptococcus pyogenes can cause local infection that may progress to sepsis. There are more than 200 serotypes of S. pyogenes defined according to sequence variations in the M protein. The M1 serotype is among 10 serotypes that are predominant in invasive infection. M1 protein can be released from the surface and has previously been shown to generate platelet, neutrophil, and monocyte activation. The platelet-dependent proinflammatory effects of other serotypes of M protein associated with invasive infection (M3, M5, M28, M49, and M89) are now investigated using a combination of multiparameter flow cytometry, enzyme-linked immunosorbent assay (ELISA), aggregometry, and quantitative mass spectrometry. We demonstrate that only M1, M3, and M5 protein serotypes can bind fibrinogen in plasma and mediate fibrinogen- and IgG-dependent platelet activation and aggregation, release of granule proteins, upregulation of CD62P to the platelet surface, and complex formation with neutrophils and monocytes. Neutrophil and monocyte activation, determined as upregulation of surface CD11b, is also mediated by M1, M3, and M5 protein serotypes, while M28, M49, and M89 proteins failed to mediate activation of platelets or leukocytes. Collectively, our findings reveal novel aspects of the immunomodulatory role of fibrinogen acquisition and platelet activation during streptococcal infections.
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spelling pubmed-88527002022-03-03 Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects Palm, Frida Chowdhury, Sounak Wettemark, Sara Malmström, Johan Happonen, Lotta Shannon, Oonagh Infect Immun Host Response and Inflammation Sepsis is a life-threatening complication of infection that is characterized by a dysregulated inflammatory state and disturbed hemostasis. Platelets are the main regulators of hemostasis, and they also respond to inflammation. The human pathogen Streptococcus pyogenes can cause local infection that may progress to sepsis. There are more than 200 serotypes of S. pyogenes defined according to sequence variations in the M protein. The M1 serotype is among 10 serotypes that are predominant in invasive infection. M1 protein can be released from the surface and has previously been shown to generate platelet, neutrophil, and monocyte activation. The platelet-dependent proinflammatory effects of other serotypes of M protein associated with invasive infection (M3, M5, M28, M49, and M89) are now investigated using a combination of multiparameter flow cytometry, enzyme-linked immunosorbent assay (ELISA), aggregometry, and quantitative mass spectrometry. We demonstrate that only M1, M3, and M5 protein serotypes can bind fibrinogen in plasma and mediate fibrinogen- and IgG-dependent platelet activation and aggregation, release of granule proteins, upregulation of CD62P to the platelet surface, and complex formation with neutrophils and monocytes. Neutrophil and monocyte activation, determined as upregulation of surface CD11b, is also mediated by M1, M3, and M5 protein serotypes, while M28, M49, and M89 proteins failed to mediate activation of platelets or leukocytes. Collectively, our findings reveal novel aspects of the immunomodulatory role of fibrinogen acquisition and platelet activation during streptococcal infections. American Society for Microbiology 2022-02-17 /pmc/articles/PMC8852700/ /pubmed/34898252 http://dx.doi.org/10.1128/iai.00462-21 Text en Copyright © 2022 Palm et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Host Response and Inflammation
Palm, Frida
Chowdhury, Sounak
Wettemark, Sara
Malmström, Johan
Happonen, Lotta
Shannon, Oonagh
Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title_full Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title_fullStr Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title_full_unstemmed Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title_short Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects
title_sort distinct serotypes of streptococcal m proteins mediate fibrinogen-dependent platelet activation and proinflammatory effects
topic Host Response and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8852700/
https://www.ncbi.nlm.nih.gov/pubmed/34898252
http://dx.doi.org/10.1128/iai.00462-21
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