| 1. |
- Bengtson, Sara H, et al.
(författare)
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Kinin receptor expression during Staphylococcus aureus infection.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:6, s. 2055-2063
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Tidskriftsartikel (refereegranskat)abstract
- An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community- and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteria-triggered contact activation, and conversion of bradykinin to its metabolite desArg9bradykinin. The data of the present study implicate an important and previously unknown role for kinin receptor regulation in S aureus infections.
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| 2. |
- Påhlman, Lars, et al.
(författare)
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Antimicrobial activity of fibrinogen and fibrinogen-derived peptides : a novel link between coagulation and innate immunity
- 2013
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 930-939
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Tidskriftsartikel (refereegranskat)abstract
- Fibrinogen is a key player in the blood coagulation system, and is upon activation with thrombin converted into fibrin that subsequently forms a fibrin clot. In the present study, we investigated the role of fibrinogen in the early innate immune response. Here we show that the viability of fibrinogen-binding bacteria is affected in human plasma activated with thrombin. Moreover, we found that the peptide fragment GHR28 released from the β-chain of fibrinogen has antimicrobial activity against bacteria that bind fibrinogen to their surface, whereas non-binding strains are unaffected. Notably, bacterial killing was detected in Group A Streptococcus bacteria entrapped in a fibrin clot, suggesting that fibrinogen and coagulation is involved in the early innate immune system to quickly wall off and neutralise invading pathogens.
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| 3. |
- Påhlman, Lisa, et al.
(författare)
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M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes
- 2007
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Ingår i: Microbiology. - : Microbiology Society. - 1465-2080 .- 1350-0872. ; 153, s. 2458-2464
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Tidskriftsartikel (refereegranskat)abstract
- Invasive infections caused by the important pathogen Streptococcus pyogenes are often associated with disturbed blood coagulation in the human host, and may in severe cases develop into the life-threatening condition disseminated intravascular coagulation. In this study, the addition of M1 protein to human blood or purified peripheral blood mononuclear cells led to a dose-dependent increase of pro-coagulant activity, which was mediated by an upregulation of tissue factor on monocytes. Analysis of the resulting clots by transmission electron microscopy revealed that the cells were covered with a fibrin network that seemed to originate from the cell surface. Taken together, the results imply an important role for M proteins in the induction of haemostatic disorders in invasive streptococcal infectious diseases.
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| 4. |
- Påhlman, Lisa, et al.
(författare)
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Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation.
- 2008
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 10:2, s. 404-414
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes of the M1 serotype is commonly associated with large outbreaks of invasive streptococcal infections and development of streptococcal toxic shock syndrome (STSS). The pathogenesis behind these infections is believed to involve bacterial superantigens that induce potent inflammatory responses, but the reason why strains of the M1 serotype are over-represented in STSS is still not understood. In the present investigation, we show that a highly purified soluble form of the M1 protein from S. pyogenes, which lacks the membrane-spanning region, is a potent inducer of T cell proliferation and release of Th1 type cytokines. M1 protein-evoked T cell proliferation was HLA class II-dependent but not MHC-restricted, did not require intracellular processing and was Vβ-restricted. Extensive mass spectrometry studies indicated that there were no other detectable proteins in the preparation. Taken together, our data demonstrate that soluble M1 protein is a novel streptococcal superantigen, which likely contributes to the excessive T cell activation and hyperinflammatory response seen in severe invasive streptococcal infections.
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| 5. |
- Påhlman, Lisa, et al.
(författare)
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Thrombin activatable fibrinolysis inhibitor binds to Streptococcus pyogenes by interacting with collagen-like surface proteins A and B.
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 282:34, s. 24873-24881
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Tidskriftsartikel (refereegranskat)abstract
- Regulation of proteolysis is a critical element of the host immune system and plays an important role in the induction of pro- and anti-inflammatory reactions in response to infection. Some bacterial species take advantage of these processes and recruit host proteinases to their surface in order to counteract the host attack. Here we show that Thrombin-activatable Fibrinolysis Inhibitor (TAFI), a zinc-dependent procarboxypeptidase, binds to the surface of group A streptococci of an M41 serotype. The interaction is mediated by the streptococcal collagen-like surface proteins A and B (Sc1A and Sc1B), and the streptococcal-associated TAFI is then processed at the bacterial surface via plasmin and thrombin-thrombomodulin. These findings suggest an important role for TAFI in the modulation of host responses by streptococci.
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