Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses
Staphylococcus aureus can cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To dev...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01579/full |
| _version_ | 1818387502738702336 |
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| author | Agnes Bonifacius Oliver Goldmann Stefan Floess Silva Holtfreter Philippe A. Robert Philippe A. Robert Maria Nordengrün Friederike Kruse Matthias Lochner Matthias Lochner Christine S. Falk Christine S. Falk Ingo Schmitz Ingo Schmitz Ingo Schmitz Barbara M. Bröker Eva Medina Jochen Huehn |
| author_facet | Agnes Bonifacius Oliver Goldmann Stefan Floess Silva Holtfreter Philippe A. Robert Philippe A. Robert Maria Nordengrün Friederike Kruse Matthias Lochner Matthias Lochner Christine S. Falk Christine S. Falk Ingo Schmitz Ingo Schmitz Ingo Schmitz Barbara M. Bröker Eva Medina Jochen Huehn |
| author_sort | Agnes Bonifacius |
| collection | DOAJ |
| description | Staphylococcus aureus can cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To develop such novel treatment approaches, a better understanding of the bacterial virulence and immune evasion mechanisms and their potential effects on immune-based therapies is essential. One important staphylococcal virulence factor is alpha-toxin, which is able to disrupt the epithelial barrier in order to establish infection. In addition, alpha-toxin has been reported to modulate other cell types including immune cells. Since CD4+ T cell-mediated immunity is required for protection against S. aureus infection, we were interested in the ability of alpha-toxin to directly modulate CD4+ T cells. To address this, murine naïve CD4+ T cells were differentiated in vitro into effector T cell subsets in the presence of alpha-toxin. Interestingly, alpha-toxin induced death of Th1-polarized cells, while cells polarized under Th17 conditions showed a high resistance toward increasing concentrations of this toxin. These effects could neither be explained by differential expression of the cellular alpha-toxin receptor ADAM10 nor by differential activation of caspases, but might result from an increased susceptibility of Th1 cells toward Ca2+-mediated activation-induced cell death. In accordance with the in vitro findings, an alpha-toxin-dependent decrease of Th1 and concomitant increase of Th17 cells was observed in vivo during S. aureus bacteremia. Interestingly, corresponding subsets of innate lymphoid cells and γδ T cells were similarly affected, suggesting a more general effect of alpha-toxin on the modulation of type 1 and type 3 immune responses. In conclusion, we have identified a novel alpha-toxin-dependent immunomodulatory strategy of S. aureus, which can directly act on CD4+ T cells and might be exploited for the development of novel immune-based therapeutic approaches to treat infections with antibiotic-resistant S. aureus strains. |
| first_indexed | 2024-12-14T04:10:58Z |
| format | Article |
| id | doaj.art-ecb0f7bd7d2c4295a7d1dae990335be1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T04:10:58Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ecb0f7bd7d2c4295a7d1dae990335be12022-12-21T23:17:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01579499243Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune ResponsesAgnes Bonifacius0Oliver Goldmann1Stefan Floess2Silva Holtfreter3Philippe A. Robert4Philippe A. Robert5Maria Nordengrün6Friederike Kruse7Matthias Lochner8Matthias Lochner9Christine S. Falk10Christine S. Falk11Ingo Schmitz12Ingo Schmitz13Ingo Schmitz14Barbara M. Bröker15Eva Medina16Jochen Huehn17Department Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Infection Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Immunology, University Medicine Greifswald, Greifswald, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment of Immunology, University Medicine Greifswald, Greifswald, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research; A Joint Venture Between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hanover, GermanyInstitute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hanover, GermanyInstitute of Transplant Immunology, Hannover Medical School, Hanover, GermanyDZIF, German Center for Infectious Diseases, TTU-IICH Hannover-Braunschweig Site, Hanover, GermanyDepartment Systems-Oriented Immunology and Inflammation Research, Helmholtz Centre for Infection Research, Braunschweig, Germany0Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany1Department of Molecular Immunology, Ruhr-University Bochum, Bochum, GermanyDepartment of Immunology, University Medicine Greifswald, Greifswald, GermanyDepartment Infection Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyDepartment Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, GermanyStaphylococcus aureus can cause life-threatening diseases, and hospital- as well as community-associated antibiotic-resistant strains are an emerging global public health problem. Therefore, prophylactic vaccines or immune-based therapies are considered as alternative treatment opportunities. To develop such novel treatment approaches, a better understanding of the bacterial virulence and immune evasion mechanisms and their potential effects on immune-based therapies is essential. One important staphylococcal virulence factor is alpha-toxin, which is able to disrupt the epithelial barrier in order to establish infection. In addition, alpha-toxin has been reported to modulate other cell types including immune cells. Since CD4+ T cell-mediated immunity is required for protection against S. aureus infection, we were interested in the ability of alpha-toxin to directly modulate CD4+ T cells. To address this, murine naïve CD4+ T cells were differentiated in vitro into effector T cell subsets in the presence of alpha-toxin. Interestingly, alpha-toxin induced death of Th1-polarized cells, while cells polarized under Th17 conditions showed a high resistance toward increasing concentrations of this toxin. These effects could neither be explained by differential expression of the cellular alpha-toxin receptor ADAM10 nor by differential activation of caspases, but might result from an increased susceptibility of Th1 cells toward Ca2+-mediated activation-induced cell death. In accordance with the in vitro findings, an alpha-toxin-dependent decrease of Th1 and concomitant increase of Th17 cells was observed in vivo during S. aureus bacteremia. Interestingly, corresponding subsets of innate lymphoid cells and γδ T cells were similarly affected, suggesting a more general effect of alpha-toxin on the modulation of type 1 and type 3 immune responses. In conclusion, we have identified a novel alpha-toxin-dependent immunomodulatory strategy of S. aureus, which can directly act on CD4+ T cells and might be exploited for the development of novel immune-based therapeutic approaches to treat infections with antibiotic-resistant S. aureus strains.https://www.frontiersin.org/article/10.3389/fimmu.2020.01579/fullStaphylococcus aureusCD4+ T cellsalpha-toxininnate lymphoid cellsγδ T cells |
| spellingShingle | Agnes Bonifacius Oliver Goldmann Stefan Floess Silva Holtfreter Philippe A. Robert Philippe A. Robert Maria Nordengrün Friederike Kruse Matthias Lochner Matthias Lochner Christine S. Falk Christine S. Falk Ingo Schmitz Ingo Schmitz Ingo Schmitz Barbara M. Bröker Eva Medina Jochen Huehn Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses Frontiers in Immunology Staphylococcus aureus CD4+ T cells alpha-toxin innate lymphoid cells γδ T cells |
| title | Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses |
| title_full | Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses |
| title_fullStr | Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses |
| title_full_unstemmed | Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses |
| title_short | Staphylococcus aureus Alpha-Toxin Limits Type 1 While Fostering Type 3 Immune Responses |
| title_sort | staphylococcus aureus alpha toxin limits type 1 while fostering type 3 immune responses |
| topic | Staphylococcus aureus CD4+ T cells alpha-toxin innate lymphoid cells γδ T cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01579/full |
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