T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection
The enzyme acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and is thereby involved in several cellular processes such as differentiation, proliferation, and apoptosis in different cell types. However, the function of ASM in T cells is still not well characterized. Here, we used T ce...
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doaj-f0cbd1f9f24b4f95a252a9b07bcd21c62020-11-25T01:23:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01225454364T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii InfectionMatthias Hose0Anne Günther1Hanna Abberger2Salina Begum3Marek Korencak4Katrin A. Becker5Jan Buer6Astrid M. Westendorf7Wiebke Hansen8Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Molecular Biology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute for HIV Research, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Molecular Biology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyInstitute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, GermanyThe enzyme acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and is thereby involved in several cellular processes such as differentiation, proliferation, and apoptosis in different cell types. However, the function of ASM in T cells is still not well characterized. Here, we used T cell-specific ASM overexpressing mice (t-ASM/CD4cre) to clarify the impact of cell-intrinsic ASM activity on T cell function in vitro and in vivo. We showed that t-ASM/CD4cre mice exhibit decreased frequencies of Foxp3+ T regulatory cells (Tregs) within the spleen. Enforced T cell-specific ASM expression resulted in less efficient induction of Tregs and promoted differentiation of CD4+CD25− naïve T cells into IFN-γ producing Th1 cells in vitro. Further analysis revealed that ASM-overexpressing T cells from t-ASM/CD4cre mice show elevated T cell receptor (TCR) signaling activity accompanied with increased proliferation upon stimulation in vitro. Plasmodium yoelii infection of t-ASM/CD4cre mice resulted in enhanced T cell activation and was associated with reduced parasitemia in comparison to infected control mice. Hence, our results provide evidence that ASM activity modulates T cell function in vitro and in vivo.https://www.frontiersin.org/article/10.3389/fimmu.2019.01225/fullsphingolipidsacid sphingomyelinaseT cellsT cell activationmalaria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthias Hose Anne Günther Hanna Abberger Salina Begum Marek Korencak Katrin A. Becker Jan Buer Astrid M. Westendorf Wiebke Hansen |
spellingShingle |
Matthias Hose Anne Günther Hanna Abberger Salina Begum Marek Korencak Katrin A. Becker Jan Buer Astrid M. Westendorf Wiebke Hansen T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection Frontiers in Immunology sphingolipids acid sphingomyelinase T cells T cell activation malaria |
author_facet |
Matthias Hose Anne Günther Hanna Abberger Salina Begum Marek Korencak Katrin A. Becker Jan Buer Astrid M. Westendorf Wiebke Hansen |
author_sort |
Matthias Hose |
title |
T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection |
title_short |
T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection |
title_full |
T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection |
title_fullStr |
T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection |
title_full_unstemmed |
T Cell-Specific Overexpression of Acid Sphingomyelinase Results in Elevated T Cell Activation and Reduced Parasitemia During Plasmodium yoelii Infection |
title_sort |
t cell-specific overexpression of acid sphingomyelinase results in elevated t cell activation and reduced parasitemia during plasmodium yoelii infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-05-01 |
description |
The enzyme acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and is thereby involved in several cellular processes such as differentiation, proliferation, and apoptosis in different cell types. However, the function of ASM in T cells is still not well characterized. Here, we used T cell-specific ASM overexpressing mice (t-ASM/CD4cre) to clarify the impact of cell-intrinsic ASM activity on T cell function in vitro and in vivo. We showed that t-ASM/CD4cre mice exhibit decreased frequencies of Foxp3+ T regulatory cells (Tregs) within the spleen. Enforced T cell-specific ASM expression resulted in less efficient induction of Tregs and promoted differentiation of CD4+CD25− naïve T cells into IFN-γ producing Th1 cells in vitro. Further analysis revealed that ASM-overexpressing T cells from t-ASM/CD4cre mice show elevated T cell receptor (TCR) signaling activity accompanied with increased proliferation upon stimulation in vitro. Plasmodium yoelii infection of t-ASM/CD4cre mice resulted in enhanced T cell activation and was associated with reduced parasitemia in comparison to infected control mice. Hence, our results provide evidence that ASM activity modulates T cell function in vitro and in vivo. |
topic |
sphingolipids acid sphingomyelinase T cells T cell activation malaria |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.01225/full |
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