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Listeria monocytoge...
Listeria monocytogenes induces T cell receptor unresponsiveness through pore-forming toxin listeriolysin O
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- Gekara, Nelson O. (författare)
- Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
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- Zietara, Natalia (författare)
- Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
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- Geffers, Robert (författare)
- Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
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- Weiss, Siegfried (författare)
- Molecular Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany
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(creator_code:org_t)
- Oxford University Press, 2010
- 2010
- Engelska.
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 202:11, s. 1698-1707
- Relaterad länk:
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https://doi.org/10.1...
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: The success of many pathogens relies on their ability to circumvent the innate and adaptive immune defenses. How bacterial pathogens subvert adaptive immune defenses is not clear. Cholesterol-dependent cytolysins (CDCs) represent an expansive family of homologous pore-forming toxins that are produced by more than 20 gram-positive bacterial species. Listeriolysin O (LLO), a prototype CDC, is the main virulence factor of Listeria monocytogenes.Methods: We employed flow cytometric and microarray techniques to analyze the effect of LLO on T cell activation in vitro and in vivo.Results: In vivo and in vitro proliferation of CD4+T cells upon T cell receptor (TCR) activation was highly diminished in the presence of LLO or wild-type L. monocytogenes but not in the presence of LLO-deficient L. monocytogenes. This block in T cell proliferation was specific to T cell activation via the TCR and not by phorbol 12-myristate 13-acetate-ionomycin, which bypasses the proximal TCR signaling event. The results of microarray analysis suggest that LLO-induced T cell unresponsiveness is due to the induction of a calcium-nuclear factor of activated T cells-dependent transcriptional program that drives the expression of negative regulators of TCR signaling.Conclusion: These findings provide important insights into how bacterial toxins silence adaptive immune responses and thus enable prolonged survival of the pathogen in the host.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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