Innate Immune Training of Human Macrophages by Cathelicidin Analogs
Trained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.777530/full |
| _version_ | 1818013271796482048 |
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| author | Albert van Dijk Jennifer Anten Anne Bakker Noah Evers Anna T. Hoekstra Jung-Chin Chang Maaike R. Scheenstra Edwin J. A. Veldhuizen Mihai G. Netea Celia R. Berkers Celia R. Berkers Henk P. Haagsman |
| author_facet | Albert van Dijk Jennifer Anten Anne Bakker Noah Evers Anna T. Hoekstra Jung-Chin Chang Maaike R. Scheenstra Edwin J. A. Veldhuizen Mihai G. Netea Celia R. Berkers Celia R. Berkers Henk P. Haagsman |
| author_sort | Albert van Dijk |
| collection | DOAJ |
| description | Trained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus, we assessed the capacity of cathelicidins to induce trained immunity. PMA-differentiated THP-1 (dTHP1) cells were trained with cathelicidin analogs for 24 hours and restimulated after a 3-day rest period. DCATH-2 training of dTHP-1 cells amplified their proinflammatory cytokine response when restimulated with TLR2/4 agonists. Trained cells displayed a biased cellular metabolism towards mTOR-dependent aerobic glycolysis and long-chain fatty acid accumulation and augmented microbicidal activity. DCATH-2-induced trained immunity was inhibited by histone acetylase inhibitors, suggesting epigenetic regulation, and depended on caveolae/lipid raft-mediated uptake, MAPK p38 and purinergic signaling. To our knowledge, this is the first report of trained immunity by host defense peptides. |
| first_indexed | 2024-04-14T06:31:07Z |
| format | Article |
| id | doaj.art-d37d6ebc82eb4e7eac6d602f7bf731cf |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:31:07Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d37d6ebc82eb4e7eac6d602f7bf731cf2022-12-22T02:07:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.777530777530Innate Immune Training of Human Macrophages by Cathelicidin AnalogsAlbert van Dijk0Jennifer Anten1Anne Bakker2Noah Evers3Anna T. Hoekstra4Jung-Chin Chang5Maaike R. Scheenstra6Edwin J. A. Veldhuizen7Mihai G. Netea8Celia R. Berkers9Celia R. Berkers10Henk P. Haagsman11Division Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, NetherlandsDivision Cell Biology, Metabolism & Cancer, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Centre, Nijmegen, NetherlandsBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, NetherlandsDivision Cell Biology, Metabolism & Cancer, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsDivision Infectious Diseases and Immunology, Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, NetherlandsTrained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus, we assessed the capacity of cathelicidins to induce trained immunity. PMA-differentiated THP-1 (dTHP1) cells were trained with cathelicidin analogs for 24 hours and restimulated after a 3-day rest period. DCATH-2 training of dTHP-1 cells amplified their proinflammatory cytokine response when restimulated with TLR2/4 agonists. Trained cells displayed a biased cellular metabolism towards mTOR-dependent aerobic glycolysis and long-chain fatty acid accumulation and augmented microbicidal activity. DCATH-2-induced trained immunity was inhibited by histone acetylase inhibitors, suggesting epigenetic regulation, and depended on caveolae/lipid raft-mediated uptake, MAPK p38 and purinergic signaling. To our knowledge, this is the first report of trained immunity by host defense peptides.https://www.frontiersin.org/articles/10.3389/fimmu.2022.777530/fullhost defense peptidecathelicidinmacrophagetrained immunityimmunomodulationmetabolomics |
| spellingShingle | Albert van Dijk Jennifer Anten Anne Bakker Noah Evers Anna T. Hoekstra Jung-Chin Chang Maaike R. Scheenstra Edwin J. A. Veldhuizen Mihai G. Netea Celia R. Berkers Celia R. Berkers Henk P. Haagsman Innate Immune Training of Human Macrophages by Cathelicidin Analogs Frontiers in Immunology host defense peptide cathelicidin macrophage trained immunity immunomodulation metabolomics |
| title | Innate Immune Training of Human Macrophages by Cathelicidin Analogs |
| title_full | Innate Immune Training of Human Macrophages by Cathelicidin Analogs |
| title_fullStr | Innate Immune Training of Human Macrophages by Cathelicidin Analogs |
| title_full_unstemmed | Innate Immune Training of Human Macrophages by Cathelicidin Analogs |
| title_short | Innate Immune Training of Human Macrophages by Cathelicidin Analogs |
| title_sort | innate immune training of human macrophages by cathelicidin analogs |
| topic | host defense peptide cathelicidin macrophage trained immunity immunomodulation metabolomics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.777530/full |
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