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

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posted on 2024-11-16, 02:03 authored by Diane LyDiane Ly, Jude Taylor, James Tsatsaronis, Mercedes M Monteleone, Amanda Skora, Cortny Donald, Tracy Maddocks, Victor Nizet, Nicholas P West, Marie RansonMarie Ranson, Mark Walker, Jason McArthur, Martina Sanderson-SmithMartina Sanderson-Smith
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.

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Defining the role of plasminogen activation in group A streptococcal invasive disease

National Health and Medical Research Council

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History

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.

Journal title

Journal of Innate Immunity

Volume

6

Issue

2

Pagination

240-250

Language

English

RIS ID

81543

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