Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previo...

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Bibliographic Details
Published in:PLoS pathogens 2008-09, Vol.4 (9), p.e1000149-e1000149
Main Authors: Kahn, Fredrik, Mörgelin, Matthias, Shannon, Oonagh, Norrby-Teglund, Anna, Herwald, Heiko, Olin, Anders I, Björck, Lars
Format: Article
Language:English
Subjects:
Antibodies, Bacterial - immunology
Antigens, Bacterial - immunology
Bacterial Outer Membrane Proteins - immunology
Bacteriology
Basic Medicine
Carrier Proteins - immunology
Cells, Cultured
Fibrinogen - metabolism
Hospitals
Humans
Immunoglobulin G
Immunology/Cellular Microbiology and Pathogenesis
Immunology/Immune Response
Immunology/Leukocyte Activation
Infections
Infectious Diseases/Bacterial Infections
Inflammation - etiology
Inflammation - immunology
Inflammation - microbiology
Intensive care
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Microbiology in the medical area
Mikrobiologi inom det medicinska området
Mortality
Neutrophils - microbiology
Proteins
Statistical methods
Streptococcal Infections - pathology
Streptococcus pyogenes
Streptococcus pyogenes - immunology
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Summary:Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1000149