Dimethyl itaconate induces long-term innate immune responses and confers protection against infection
Summary: Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of i...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723006691 |
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| author | Anaísa V. Ferreira Sarantos Kostidis Laszlo A. Groh Valerie A.C.M. Koeken Mariolina Bruno Ilayda Baydemir Gizem Kilic Özlem Bulut Theano Andriopoulou Victoria Spanou Kalliopi D. Synodinou Theologia Gkavogianni Simone J.C.F.M. Moorlag L. Charlotte de Bree Vera P. Mourits Vasiliki Matzaraki Werner J.H. Koopman Frank L. van de Veerdonk Georgios Renieris Martin Giera Evangelos J. Giamarellos-Bourboulis Boris Novakovic Jorge Domínguez-Andrés |
| author_facet | Anaísa V. Ferreira Sarantos Kostidis Laszlo A. Groh Valerie A.C.M. Koeken Mariolina Bruno Ilayda Baydemir Gizem Kilic Özlem Bulut Theano Andriopoulou Victoria Spanou Kalliopi D. Synodinou Theologia Gkavogianni Simone J.C.F.M. Moorlag L. Charlotte de Bree Vera P. Mourits Vasiliki Matzaraki Werner J.H. Koopman Frank L. van de Veerdonk Georgios Renieris Martin Giera Evangelos J. Giamarellos-Bourboulis Boris Novakovic Jorge Domínguez-Andrés |
| author_sort | Anaísa V. Ferreira |
| collection | DOAJ |
| description | Summary: Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of inflammation and widely employed as an alternative to the endogenous metabolite, can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. Dimethyl itaconate alters glycolytic and mitochondrial energetic metabolism, ultimately leading to increased responsiveness to microbial ligand stimulation. Subsequently, mice treated with dimethyl itaconate present increased survival to infection with Staphylococcus aureus. Additionally, itaconate levels in human plasma correlate with enhanced ex vivo pro-inflammatory cytokine production. Collectively, these findings demonstrate that dimethyl itaconate displays short-term anti-inflammatory characteristics and the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of dimethyl itaconate is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context. |
| first_indexed | 2024-03-13T04:55:36Z |
| format | Article |
| id | doaj.art-6e7649ccdf4846afb0796f373689a5d6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T04:55:36Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6e7649ccdf4846afb0796f373689a5d62023-06-18T05:01:33ZengElsevierCell Reports2211-12472023-06-01426112658Dimethyl itaconate induces long-term innate immune responses and confers protection against infectionAnaísa V. Ferreira0Sarantos Kostidis1Laszlo A. Groh2Valerie A.C.M. Koeken3Mariolina Bruno4Ilayda Baydemir5Gizem Kilic6Özlem Bulut7Theano Andriopoulou8Victoria Spanou9Kalliopi D. Synodinou10Theologia Gkavogianni11Simone J.C.F.M. Moorlag12L. Charlotte de Bree13Vera P. Mourits14Vasiliki Matzaraki15Werner J.H. Koopman16Frank L. van de Veerdonk17Georgios Renieris18Martin Giera19Evangelos J. Giamarellos-Bourboulis20Boris Novakovic21Jorge Domínguez-Andrés22Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the Netherlands; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal; Corresponding authorCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA Leiden, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the Netherlands; TWINCORE, a Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, Germany; Centre for Individualised Infection Medicine (CiiM), Department of Computational Biology for Individualised Infection Medicine, a Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), 30625 Hannover, GermanyDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, GreeceDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the NetherlandsDepartment of Pediatrics, Amalia Children’s Hospital, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, the NetherlandsDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, GreeceCenter for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA Leiden, the Netherlands4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, GreeceMurdoch Children’s Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, AustraliaDepartment of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Centre, 6500HB Nijmegen, the Netherlands; Corresponding authorSummary: Itaconate is an immunomodulatory metabolite produced by immune cells under microbial stimulation and certain pro-inflammatory conditions and triggers antioxidant and anti-inflammatory responses. We show that dimethyl itaconate, a derivative of itaconate previously linked to suppression of inflammation and widely employed as an alternative to the endogenous metabolite, can induce long-term transcriptional, epigenomic, and metabolic changes, characteristic of trained immunity. Dimethyl itaconate alters glycolytic and mitochondrial energetic metabolism, ultimately leading to increased responsiveness to microbial ligand stimulation. Subsequently, mice treated with dimethyl itaconate present increased survival to infection with Staphylococcus aureus. Additionally, itaconate levels in human plasma correlate with enhanced ex vivo pro-inflammatory cytokine production. Collectively, these findings demonstrate that dimethyl itaconate displays short-term anti-inflammatory characteristics and the capacity to induce long-term trained immunity. This pro-and anti-inflammatory dichotomy of dimethyl itaconate is likely to induce complex immune responses and should be contemplated when considering itaconate derivatives in a therapeutic context.http://www.sciencedirect.com/science/article/pii/S2211124723006691CP: Immunology |
| spellingShingle | Anaísa V. Ferreira Sarantos Kostidis Laszlo A. Groh Valerie A.C.M. Koeken Mariolina Bruno Ilayda Baydemir Gizem Kilic Özlem Bulut Theano Andriopoulou Victoria Spanou Kalliopi D. Synodinou Theologia Gkavogianni Simone J.C.F.M. Moorlag L. Charlotte de Bree Vera P. Mourits Vasiliki Matzaraki Werner J.H. Koopman Frank L. van de Veerdonk Georgios Renieris Martin Giera Evangelos J. Giamarellos-Bourboulis Boris Novakovic Jorge Domínguez-Andrés Dimethyl itaconate induces long-term innate immune responses and confers protection against infection Cell Reports CP: Immunology |
| title | Dimethyl itaconate induces long-term innate immune responses and confers protection against infection |
| title_full | Dimethyl itaconate induces long-term innate immune responses and confers protection against infection |
| title_fullStr | Dimethyl itaconate induces long-term innate immune responses and confers protection against infection |
| title_full_unstemmed | Dimethyl itaconate induces long-term innate immune responses and confers protection against infection |
| title_short | Dimethyl itaconate induces long-term innate immune responses and confers protection against infection |
| title_sort | dimethyl itaconate induces long term innate immune responses and confers protection against infection |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723006691 |
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