Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced c...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-11-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1641387 |
| _version_ | 1819105913662865408 |
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| author | Edda Blümel Andreas Willerslev-Olsen Maria Gluud Lise M. Lindahl Simon Fredholm Claudia Nastasi Thorbjørn Krejsgaard Bas G. J. Surewaard Sergei B. Koralov Tengpeng Hu Jenny L. Persson Charlotte Menné Bonefeld Carsten Geisler Lars Iversen Jürgen C. Becker Mads Hald Andersen Anders Woetmann Terkild Brink Buus Niels Ødum |
| author_facet | Edda Blümel Andreas Willerslev-Olsen Maria Gluud Lise M. Lindahl Simon Fredholm Claudia Nastasi Thorbjørn Krejsgaard Bas G. J. Surewaard Sergei B. Koralov Tengpeng Hu Jenny L. Persson Charlotte Menné Bonefeld Carsten Geisler Lars Iversen Jürgen C. Becker Mads Hald Andersen Anders Woetmann Terkild Brink Buus Niels Ødum |
| author_sort | Edda Blümel |
| collection | DOAJ |
| description | Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL. |
| first_indexed | 2024-12-22T02:29:48Z |
| format | Article |
| id | doaj.art-85e3c47951f844e3992b9edf776ee97d |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-22T02:29:48Z |
| publishDate | 2019-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-85e3c47951f844e3992b9edf776ee97d2022-12-21T18:41:55ZengTaylor & Francis GroupOncoImmunology2162-402X2019-11-0181110.1080/2162402X.2019.16413871641387Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphomaEdda Blümel0Andreas Willerslev-Olsen1Maria Gluud2Lise M. Lindahl3Simon Fredholm4Claudia Nastasi5Thorbjørn Krejsgaard6Bas G. J. Surewaard7Sergei B. Koralov8Tengpeng Hu9Jenny L. Persson10Charlotte Menné Bonefeld11Carsten Geisler12Lars Iversen13Jürgen C. Becker14Mads Hald Andersen15Anders Woetmann16Terkild Brink Buus17Niels Ødum18University of CopenhagenUniversity of CopenhagenUniversity of CopenhagenAarhus University HospitalUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenSnyder Institute for Chronic Diseases, University of CalgaryNew York University School of MedicineUniversity of CopenhagenLund UniversityUniversity of CopenhagenUniversity of CopenhagenAarhus University HospitalUniversity Hospital Essen and Deutsches Krebsforschungszentrum (DKFZ)University of CopenhagenUniversity of CopenhagenUniversity of CopenhagenUniversity of CopenhagenStaphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.http://dx.doi.org/10.1080/2162402X.2019.1641387cutaneous t-cell lymphomastaphylococcus aureusalpha-toxindisintegrin and metalloproteinase domain-containing protein 10 |
| spellingShingle | Edda Blümel Andreas Willerslev-Olsen Maria Gluud Lise M. Lindahl Simon Fredholm Claudia Nastasi Thorbjørn Krejsgaard Bas G. J. Surewaard Sergei B. Koralov Tengpeng Hu Jenny L. Persson Charlotte Menné Bonefeld Carsten Geisler Lars Iversen Jürgen C. Becker Mads Hald Andersen Anders Woetmann Terkild Brink Buus Niels Ødum Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma OncoImmunology cutaneous t-cell lymphoma staphylococcus aureus alpha-toxin disintegrin and metalloproteinase domain-containing protein 10 |
| title | Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma |
| title_full | Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma |
| title_fullStr | Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma |
| title_full_unstemmed | Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma |
| title_short | Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma |
| title_sort | staphylococcal alpha toxin tilts the balance between malignant and non malignant cd4 t cells in cutaneous t cell lymphoma |
| topic | cutaneous t-cell lymphoma staphylococcus aureus alpha-toxin disintegrin and metalloproteinase domain-containing protein 10 |
| url | http://dx.doi.org/10.1080/2162402X.2019.1641387 |
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