title: Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated neutrophil killing.
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: Illawarra Health and Medical Research Institute and School of Biological Sciences, University of Wollongong, Wollongong, N.S.W., Australia.
authors: Diane
authors: D
authors: Ly
authors: Jude M
authors: JM
authors: Taylor
authors: James A
authors: JA
authors: Tsatsaronis
authors: Mercedes M
authors: MM
authors: Monteleone
authors: Amanda S
authors: AS
authors: Skora
authors: Cortny A
authors: CA
authors: Donald
authors: Tracy
authors: T
authors: Maddocks
authors: Victor
authors: V
authors: Nizet
authors: Nicholas P
authors: NP
authors: West
authors: Marie
authors: M
authors: Ranson
authors: Mark J
authors: MJ
authors: Walker
authors: Jason D
authors: JD
authors: McArthur
authors: Martina L
authors: ML
authors: Sanderson-Smith
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003179:Complement C3b / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005341:Fibrinolysin / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D008297:Male; D008822:Mice, Transgenic; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology*; D010958:Plasminogen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013290:Streptococcal Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D013300:Streptokinase / Q000276:immunology / Q000378:metabolism
chemical_list: D003179:Complement C3b; D010958:Plasminogen; D013300:Streptokinase; D005341:Fibrinolysin
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