| 1. |
- Frick, Inga-Maria, et al.
(författare)
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Infectious Agents, the Contact System, and Innate Immunity
- 2008
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Ingår i: Progress and Challenges in Transfusion Medicine, Hemostasis, and Hemotherapy State of the Art 2008. - 9783805586597 ; , s. 60-70
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Konferensbidrag (refereegranskat)abstract
- The early host response to an infection is dependent on an efficient innate immune system. The human contact system once activated at a bacterial surface results in the induction of proinflammatory reactions and the release of antimicrobial peptides, However, under severe conditions its systemic activation A may evoke the generation of pathologic levels of kinins and a consumption of contact factors, which can both contribute to the progression of the disease and cause life-threatening complications. The present review aims to give an update on the role of the contact system in infectious diseases. (C) 2008 S. Karger GmbH, Freiburg i.Br.
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| 2. |
- Frick, Inga-Maria, et al.
(författare)
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The contact system - a novel branch of innate immunity generating antibacterial peptides
- 2006
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:23, s. 5569-5578
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Tidskriftsartikel (refereegranskat)abstract
- Activation of the contact system has two classical consequences: initiation of the intrinsic pathway of coagulation, and cleavage of high molecular weight kininogen (HK) leading to the release of bradykinin, a potent proinflammatory peptide. In human plasma, activation of the contact system at the surface of significant bacterial pathogens was found to result in further HK processing and bacterial killing. A fragment comprising the D3 domain of HK is generated, and within this fragment a sequence of 26 amino acids is mainly responsible for the antibacterial activity. A synthetic peptide covering this sequence kills several bacterial species, also at physiological salt concentration, as effectively as the classical human antibacterial peptide LL-37. Moreover, in an animal model of infection, inhibition of the contact system promotes bacterial dissemination and growth. These data identify a novel and important role for the contact system in the defence against invasive bacterial infection.
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| 3. |
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| 4. |
- 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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