The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages
As a facultative intracellular pathogen, Staphylococcus aureus invades macrophages and then promotes the cytoprotection of infected cells thus stabilizing safe niche for silent persistence. This process occurs through the upregulation of crucial antiapoptotic genes, in particular, myeloid cell leuke...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/427021 |
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| author | Joanna Koziel Katarzyna Kmiecik Daniela Chmiest Katarzyna Maresz Danuta Mizgalska Agnieszka Maciag-Gudowska Piotr Mydel Jan Potempa |
| author_facet | Joanna Koziel Katarzyna Kmiecik Daniela Chmiest Katarzyna Maresz Danuta Mizgalska Agnieszka Maciag-Gudowska Piotr Mydel Jan Potempa |
| author_sort | Joanna Koziel |
| collection | DOAJ |
| description | As a facultative intracellular pathogen, Staphylococcus aureus invades macrophages and then promotes the cytoprotection of infected cells thus stabilizing safe niche for silent persistence. This process occurs through the upregulation of crucial antiapoptotic
genes, in particular, myeloid cell leukemia-1 (MCL-1). Here, we investigated the underlying mechanism and signal transduction pathways leading to increased MCL-1 expression in infected macrophages. Live S. aureus not only stimulated de novo synthesis of Mcl-1, but also prolonged the stability of this antiapoptotic protein. Consistent with this, we proved a crucial role of Mcl-1 in S. aureus-induced cytoprotection, since silencing of MCL1 by siRNA profoundly reversed the
cytoprotection of infected cells leading to apoptosis. Increased MCL1 expression in infected cells was associated with enhanced NFκB activation and subsequent IL-6 secretion, since the inhibition of both NFκB and IL-6 signalling pathways abrogated Mcl-1 induction and cytoprotection. Finally, we confirmed our observation in vivo in murine model of septic arthritis showing the association between the severity of arthritis and Mcl-1 expression. Therefore, we propose that S. aureus is hijacking the Mcl-1-dependent inhibition of apoptosis to prevent the elimination of infected host cells, thus allowing the intracellular persistence of the pathogen, its dissemination by infected macrophages, and the progression of staphylococci diseases. |
| format | Article |
| id | doaj-art-4f57a5b39aef4907abc91bc5fdd36df5 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4f57a5b39aef4907abc91bc5fdd36df52025-08-20T03:20:16ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/427021427021The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected MacrophagesJoanna Koziel0Katarzyna Kmiecik1Daniela Chmiest2Katarzyna Maresz3Danuta Mizgalska4Agnieszka Maciag-Gudowska5Piotr Mydel6Jan Potempa7Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandBroegelmann Research Laboratory, The Gade Institute, University of Bergen, 50021 Bergen, NorwayDepartment of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Ul. Gronostajowa 7, 30-387 Kraków, PolandAs a facultative intracellular pathogen, Staphylococcus aureus invades macrophages and then promotes the cytoprotection of infected cells thus stabilizing safe niche for silent persistence. This process occurs through the upregulation of crucial antiapoptotic genes, in particular, myeloid cell leukemia-1 (MCL-1). Here, we investigated the underlying mechanism and signal transduction pathways leading to increased MCL-1 expression in infected macrophages. Live S. aureus not only stimulated de novo synthesis of Mcl-1, but also prolonged the stability of this antiapoptotic protein. Consistent with this, we proved a crucial role of Mcl-1 in S. aureus-induced cytoprotection, since silencing of MCL1 by siRNA profoundly reversed the cytoprotection of infected cells leading to apoptosis. Increased MCL1 expression in infected cells was associated with enhanced NFκB activation and subsequent IL-6 secretion, since the inhibition of both NFκB and IL-6 signalling pathways abrogated Mcl-1 induction and cytoprotection. Finally, we confirmed our observation in vivo in murine model of septic arthritis showing the association between the severity of arthritis and Mcl-1 expression. Therefore, we propose that S. aureus is hijacking the Mcl-1-dependent inhibition of apoptosis to prevent the elimination of infected host cells, thus allowing the intracellular persistence of the pathogen, its dissemination by infected macrophages, and the progression of staphylococci diseases.http://dx.doi.org/10.1155/2013/427021 |
| spellingShingle | Joanna Koziel Katarzyna Kmiecik Daniela Chmiest Katarzyna Maresz Danuta Mizgalska Agnieszka Maciag-Gudowska Piotr Mydel Jan Potempa The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages Mediators of Inflammation |
| title | The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages |
| title_full | The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages |
| title_fullStr | The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages |
| title_full_unstemmed | The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages |
| title_short | The Role of Mcl-1 in S. aureus-Induced Cytoprotection of Infected Macrophages |
| title_sort | role of mcl 1 in s aureus induced cytoprotection of infected macrophages |
| url | http://dx.doi.org/10.1155/2013/427021 |
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