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

Palm, Frida LU ; Chowdhury, Sounak LU ; Wettemark, Sara LU ; Malmström, Johan LU orcid ; Happonen, Lotta LU and Shannon, Oonagh LU (2022) In Infection and Immunity 90(2). p.1-12
Abstract

Sepsis is a life-threatening complication of infection that is characterised 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 different serotypes of S. pyogenes defined according to sequence variations in the M protein. The M1 serotype is among ten 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 pro-inflammatory effects of other serotypes of M protein... (More)

Sepsis is a life-threatening complication of infection that is characterised 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 different serotypes of S. pyogenes defined according to sequence variations in the M protein. The M1 serotype is among ten 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 pro-inflammatory effects of other serotypes of M protein associated with invasive infection (M3, M5, M28, M49 and M89) is now investigated using a combination of multiparameter flow cytometry, 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- or 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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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
90
issue
2
article number
e00462-21
pages
1 - 12
publisher
American Society for Microbiology
external identifiers
  • pmid:34898252
  • scopus:85124850634
ISSN
1098-5522
DOI
10.1128/IAI.00462-21
language
English
LU publication?
yes
id
bfba01eb-8a8c-43c6-ade5-9a1bd8864cc1
date added to LUP
2021-12-19 22:13:56
date last changed
2024-04-21 19:04:36
@article{bfba01eb-8a8c-43c6-ade5-9a1bd8864cc1,
  abstract     = {{<p>Sepsis is a life-threatening complication of infection that is characterised 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 different serotypes of S. pyogenes defined according to sequence variations in the M protein. The M1 serotype is among ten 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 pro-inflammatory effects of other serotypes of M protein associated with invasive infection (M3, M5, M28, M49 and M89) is now investigated using a combination of multiparameter flow cytometry, 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- or 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.</p>}},
  author       = {{Palm, Frida and Chowdhury, Sounak and Wettemark, Sara and Malmström, Johan and Happonen, Lotta and Shannon, Oonagh}},
  issn         = {{1098-5522}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{1--12}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Infection and Immunity}},
  title        = {{Distinct Serotypes of Streptococcal M Proteins Mediate Fibrinogen-Dependent Platelet Activation and Proinflammatory Effects}},
  url          = {{http://dx.doi.org/10.1128/IAI.00462-21}},
  doi          = {{10.1128/IAI.00462-21}},
  volume       = {{90}},
  year         = {{2022}},
}