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| 2. |
- Kahn, Fredrik, et al.
(författare)
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Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
- 2008
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Linder, Adam, et al.
(författare)
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Erysipelas Caused by Group A Streptococcus Activates the Contact System and Induces the Release of Heparin-Binding Protein.
- 2010
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 130, s. 1365-1372
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial skin infections, such as erysipelas or cellulitis, are characterized by fever and a painful erythematous rash. Despite the high prevalence of these infections, little is known about the underlying pathogenic mechanisms. This is partly due to the fact that a bacterial diagnosis is often difficult to attain. To gain insight into the pathogenesis of erysipelas, we investigated the samples obtained from infected and noninfected areas of skin from 12 patients with erysipelas. Bacterial cultures, detection of specific streptococcal antibodies in convalescent sera, and immunohistochemical analyses of biopsies indicated group A streptococcal etiology in 11 of the 12 patients. Also, electron micrographs of erythematous skin confirmed the presence of group A streptococcal cells and showed a limited solubilization of the surface-attached M protein. Degradation of high-molecular-weight kininogen and upregulation of the bradykinin-1 receptor in inflamed tissues indicated activation of the contact system in 11 patients. Analyses of release of the vasoactive heparin-binding protein (HBP) showed increased levels in the infected as compared with the noninfected areas. The results suggest that group A streptococci induce contact activation and HBP release during skin infection, which likely contribute to the symptoms seen in erysipelas: fever, pain, erythema, and edema.Journal of Investigative Dermatology advance online publication, 28 January 2010; doi:10.1038/jid.2009.437.
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| 4. |
- Shannon, Oonagh, et al.
(författare)
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Severe streptococcal infection is associated with M protein-induced platelet activation and thrombus formation.
- 2007
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 65:5, s. 1147-1157
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Tidskriftsartikel (refereegranskat)abstract
- Disturbed haemostasis is a central finding in severe Streptococcus pyogenes infection. In particular, microthrombi are found both at the local site of infection and at distant sites. Platelets are responsible for maintaining vascular function and haemostasis. We report here that M1 protein of S. pyogenes triggers immune-mediated platelet activation and thrombus formation. M1 protein is released from the bacterial surface and forms complexes with plasma fibrinogen. These complexes bind to the fibrinogen receptor on resting platelets. When these complexes also contain immunoglobulin G (IgG) against M1 protein, this will engage the Fc receptor on the platelets and activation will occur. Activation of the platelets leads to platelet aggregation and the generation of platelet-rich thrombi. Neutrophils and monocytes are in turn activated by the platelets. Platelet thrombi are deposited in the microvasculature, and aggregated platelets, IgG and M1 protein colocalize in biopsies from patients diagnosed with S. pyogenes toxic shock syndrome. This chain of events results in a procoagulant and pro-inflammatory state typical of severe S. pyogenes infection.
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| 5. |
- Westman, Johannes, et al.
(författare)
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Protein SIC secreted from Streptococcus pyogenes forms complexes with extracellular histones that boost cytokine production
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:FEB, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity relies on an effective recognition of the pathogenic microorganism as well as on endogenous danger signals. While bacteria in concert with their secreted virulence factors can cause a number of inflammatory reactions, danger signals released at the site of infection may in addition determine the amplitude of such responses and influence the outcome of the disease. Here, we report that protein SIC, Streptococcal Inhibitor of Complement, an abundant secreted protein from Streptococcus pyogenes, binds to extracellular histones, a group of danger signals released during necrotizing tissue damage. This interaction leads to the formation of large aggregates in vitro. Extracellular histones and SIC are abundantly expressed and seen colocalized in biopsies from patients with necrotizing soft-tissue infections caused by S. pyogenes. In addition, binding of SIC to histones neutralized their antimicrobial activity. Likewise, the ability of histones to induce hemolysis was inhibited in the presence of SIC. However, when added to whole blood, SIC was not able to block the pro-inflammatory effect of histones. Instead SIC boosted the histone-triggered release of a broad range of cytokines and chemokines, including IL-6, TNF-α, IL-8, IL-1β, IL-1ra, G-CSF, and IFN-γ. These results demonstrate that the interaction between SIC and histones has multiple effects on the host response to S. pyogenes infection.
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