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Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing

Journal Article


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Abstract


  • The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased bacterial survival in a humanized plasminogen mouse model of infection. These findings demonstrate that localized plasmin(ogen) plays an important role in facilitating GAS escape from the host innate immune response and increases bacterial virulence in the early stages of infection.

Authors


  •   Ly, Diane T.
  •   Taylor, Jude M. (external author)
  •   Tsatsaronis, James A. (external author)
  •   Monteleone, Mercedes M. (external author)
  •   Skora, Amanda S. (external author)
  •   Donald, Cortny A. (external author)
  •   Maddocks, Tracy A. (external author)
  •   Nizet, Victor (external author)
  •   West, Nicholas P. (external author)
  •   Ranson, Marie
  •   Walker, Mark J. (external author)
  •   McArthur, Jason D.
  •   Sanderson-Smith, Martina L.

Publication Date


  • 2014

Citation


  • Ly, D., Taylor, J. M., Tsatsaronis, J. A., Monteleone, M. M., Skora, A. S., Donald, C. A., Maddocks, T., Nizet, V., West, N. P., Ranson, M., Walker, M. J., McArthur, J. D. & Sanderson-Smith, M. L. (2014). Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing. Journal of Innate Immunity, 6 (2), 240-250.

Scopus Eid


  • 2-s2.0-84896371471

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1432&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/415

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 240

End Page


  • 250

Volume


  • 6

Issue


  • 2

Place Of Publication


  • Switzerland

Abstract


  • The globally significant human pathogen group A Streptococcus (GAS) sequesters the host protease plasmin to the cell surface during invasive disease initiation. Recent evidence has shown that localized plasmin activity prevents opsonization of several bacterial species by key components of the innate immune system in vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in degradation of complement factor C3b, and that plasminogen acquisition is associated with a decrease in C3b opsonization and neutrophil-mediated killing in vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates directly with a decrease in C3b opsonization, neutrophil phagocytosis, and increased bacterial survival in a humanized plasminogen mouse model of infection. These findings demonstrate that localized plasmin(ogen) plays an important role in facilitating GAS escape from the host innate immune response and increases bacterial virulence in the early stages of infection.

Authors


  •   Ly, Diane T.
  •   Taylor, Jude M. (external author)
  •   Tsatsaronis, James A. (external author)
  •   Monteleone, Mercedes M. (external author)
  •   Skora, Amanda S. (external author)
  •   Donald, Cortny A. (external author)
  •   Maddocks, Tracy A. (external author)
  •   Nizet, Victor (external author)
  •   West, Nicholas P. (external author)
  •   Ranson, Marie
  •   Walker, Mark J. (external author)
  •   McArthur, Jason D.
  •   Sanderson-Smith, Martina L.

Publication Date


  • 2014

Citation


  • Ly, D., Taylor, J. M., Tsatsaronis, J. A., Monteleone, M. M., Skora, A. S., Donald, C. A., Maddocks, T., Nizet, V., West, N. P., Ranson, M., Walker, M. J., McArthur, J. D. & Sanderson-Smith, M. L. (2014). Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing. Journal of Innate Immunity, 6 (2), 240-250.

Scopus Eid


  • 2-s2.0-84896371471

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1432&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/415

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 240

End Page


  • 250

Volume


  • 6

Issue


  • 2

Place Of Publication


  • Switzerland