Glutathione Metabolism Contributes to the Induction of Trained Immunity
The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has b...
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| Format: | Article |
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/971 |
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| author | Anaisa V. Ferreira Valerie A. C. M. Koeken Vasiliki Matzaraki Sarantos Kostidis Juan Carlos Alarcon-Barrera L. Charlotte J. de Bree Simone J. C. F. M. Moorlag Vera P. Mourits Boris Novakovic Martin A. Giera Mihai G. Netea Jorge Domínguez-Andrés |
| author_facet | Anaisa V. Ferreira Valerie A. C. M. Koeken Vasiliki Matzaraki Sarantos Kostidis Juan Carlos Alarcon-Barrera L. Charlotte J. de Bree Simone J. C. F. M. Moorlag Vera P. Mourits Boris Novakovic Martin A. Giera Mihai G. Netea Jorge Domínguez-Andrés |
| author_sort | Anaisa V. Ferreira |
| collection | DOAJ |
| description | The innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did not influence cell responsiveness; the modulation of glutathione levels reduced pro-inflammatory cytokine production in human monocytes. Single nucleotide polymorphisms (SNPs) in genes involved in glutathione metabolism were found to be associated with changes in pro-inflammatory cytokine production capacity upon trained immunity. Also, plasma glutathione concentrations were positively associated with ex vivo IL-1β production, a biomarker of trained immunity, produced by monocytes of BCG-vaccinated individuals. In conclusion, glutathione metabolism is involved in the induction of trained immunity, and future studies are warranted to explore its functional consequences in human diseases. |
| first_indexed | 2024-03-10T12:08:02Z |
| format | Article |
| id | doaj.art-d36d52f9a9ed45fbbd5ac61494727205 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:08:02Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d36d52f9a9ed45fbbd5ac614947272052023-11-21T16:29:33ZengMDPI AGCells2073-44092021-04-0110597110.3390/cells10050971Glutathione Metabolism Contributes to the Induction of Trained ImmunityAnaisa V. Ferreira0Valerie A. C. M. Koeken1Vasiliki Matzaraki2Sarantos Kostidis3Juan Carlos Alarcon-Barrera4L. Charlotte J. de Bree5Simone J. C. F. M. Moorlag6Vera P. Mourits7Boris Novakovic8Martin A. Giera9Mihai G. Netea10Jorge Domínguez-Andrés11Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsEpigenetics Research, Murdoch Children’s Research Institute, Parkville, VIC 3052, AustraliaCenter for Proteomics and Metabolomics, Leiden University Medical Center (LUMC), 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The NetherlandsThe innate immune system displays heterologous memory characteristics, which are characterized by stronger responses to a secondary challenge. This phenomenon termed trained immunity relies on epigenetic and metabolic rewiring of innate immune cells. As reactive oxygen species (ROS) production has been associated with the trained immunity phenotype, we hypothesized that the increased ROS levels and the main intracellular redox molecule glutathione play a role in the induction of trained immunity. Here we show that pharmacological inhibition of ROS in an in vitro model of trained immunity did not influence cell responsiveness; the modulation of glutathione levels reduced pro-inflammatory cytokine production in human monocytes. Single nucleotide polymorphisms (SNPs) in genes involved in glutathione metabolism were found to be associated with changes in pro-inflammatory cytokine production capacity upon trained immunity. Also, plasma glutathione concentrations were positively associated with ex vivo IL-1β production, a biomarker of trained immunity, produced by monocytes of BCG-vaccinated individuals. In conclusion, glutathione metabolism is involved in the induction of trained immunity, and future studies are warranted to explore its functional consequences in human diseases.https://www.mdpi.com/2073-4409/10/5/971glutathionetrained immunitymacrophagesmetabolisminnate immune memory |
| spellingShingle | Anaisa V. Ferreira Valerie A. C. M. Koeken Vasiliki Matzaraki Sarantos Kostidis Juan Carlos Alarcon-Barrera L. Charlotte J. de Bree Simone J. C. F. M. Moorlag Vera P. Mourits Boris Novakovic Martin A. Giera Mihai G. Netea Jorge Domínguez-Andrés Glutathione Metabolism Contributes to the Induction of Trained Immunity Cells glutathione trained immunity macrophages metabolism innate immune memory |
| title | Glutathione Metabolism Contributes to the Induction of Trained Immunity |
| title_full | Glutathione Metabolism Contributes to the Induction of Trained Immunity |
| title_fullStr | Glutathione Metabolism Contributes to the Induction of Trained Immunity |
| title_full_unstemmed | Glutathione Metabolism Contributes to the Induction of Trained Immunity |
| title_short | Glutathione Metabolism Contributes to the Induction of Trained Immunity |
| title_sort | glutathione metabolism contributes to the induction of trained immunity |
| topic | glutathione trained immunity macrophages metabolism innate immune memory |
| url | https://www.mdpi.com/2073-4409/10/5/971 |
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