Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity
Summary: Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immun...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224002517 |
| _version_ | 1797320979935920128 |
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| author | Cian J.H. Horneck Johnston Anna E. Ledwith Mimmi L.E. Lundahl Hugo Charles-Messance Emer E. Hackett Simon D. O’Shaughnessy Jonah Clegg Hannah Prendeville John P. McGrath Aaron M. Walsh Sarah Case Hollie Austen Byrne Parth Gautam Elaine Dempsey Sinead C. Corr Frederick J. Sheedy |
| author_facet | Cian J.H. Horneck Johnston Anna E. Ledwith Mimmi L.E. Lundahl Hugo Charles-Messance Emer E. Hackett Simon D. O’Shaughnessy Jonah Clegg Hannah Prendeville John P. McGrath Aaron M. Walsh Sarah Case Hollie Austen Byrne Parth Gautam Elaine Dempsey Sinead C. Corr Frederick J. Sheedy |
| author_sort | Cian J.H. Horneck Johnston |
| collection | DOAJ |
| description | Summary: Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse β-glucans, we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogram metabolism and thereby drive trained immunity in human monocyte-derived macrophages in vitro and mice bone marrow in vivo. Presentation of pure, non-soluble, non-aggregated WGPs led to the formation of the Dectin-1 phagocytic synapse with subsequent lysosomal mTOR activation, metabolic reprogramming, and epigenetic rewiring. Intraperitoneal or oral administration of WGP drove bone marrow myelopoiesis and improved mature macrophage responses, pointing to therapeutic and food-based strategies to drive trained immunity. Thus, the investment of a cell in a trained response relies on specific recognition of β-glucans presented on intact microbial particles through stimulation of the Dectin-1 phagocytic response. |
| first_indexed | 2024-03-08T04:50:54Z |
| format | Article |
| id | doaj.art-a82f686f0bfb42e89b2067f61614d09d |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T04:50:54Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-a82f686f0bfb42e89b2067f61614d09d2024-02-08T05:12:52ZengElsevieriScience2589-00422024-03-01273109030Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunityCian J.H. Horneck Johnston0Anna E. Ledwith1Mimmi L.E. Lundahl2Hugo Charles-Messance3Emer E. Hackett4Simon D. O’Shaughnessy5Jonah Clegg6Hannah Prendeville7John P. McGrath8Aaron M. Walsh9Sarah Case10Hollie Austen Byrne11Parth Gautam12Elaine Dempsey13Sinead C. Corr14Frederick J. Sheedy15School of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, Ireland; School of Medicine, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, IrelandSchool of Genetics & Microbiology, Trinity College, Dublin 2, IrelandSchool of Genetics & Microbiology, Trinity College, Dublin 2, Ireland; APC Microbiome Ireland, University College Cork, Cork, IrelandSchool of Biochemistry & Immunology, Trinity College, Dublin 2, Ireland; Corresponding authorSummary: Fungal β-glucans are major drivers of trained immunity which increases long-term protection against secondary infections. Heterogeneity in β-glucan source, structure, and solubility alters interaction with the phagocytic receptor Dectin-1 and could impact strategies to improve trained immunity in humans. Using a panel of diverse β-glucans, we describe the ability of a specific yeast-derived whole-glucan particle (WGP) to reprogram metabolism and thereby drive trained immunity in human monocyte-derived macrophages in vitro and mice bone marrow in vivo. Presentation of pure, non-soluble, non-aggregated WGPs led to the formation of the Dectin-1 phagocytic synapse with subsequent lysosomal mTOR activation, metabolic reprogramming, and epigenetic rewiring. Intraperitoneal or oral administration of WGP drove bone marrow myelopoiesis and improved mature macrophage responses, pointing to therapeutic and food-based strategies to drive trained immunity. Thus, the investment of a cell in a trained response relies on specific recognition of β-glucans presented on intact microbial particles through stimulation of the Dectin-1 phagocytic response.http://www.sciencedirect.com/science/article/pii/S2589004224002517PhysiologyMolecular biologyImmunology |
| spellingShingle | Cian J.H. Horneck Johnston Anna E. Ledwith Mimmi L.E. Lundahl Hugo Charles-Messance Emer E. Hackett Simon D. O’Shaughnessy Jonah Clegg Hannah Prendeville John P. McGrath Aaron M. Walsh Sarah Case Hollie Austen Byrne Parth Gautam Elaine Dempsey Sinead C. Corr Frederick J. Sheedy Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity iScience Physiology Molecular biology Immunology |
| title | Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity |
| title_full | Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity |
| title_fullStr | Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity |
| title_full_unstemmed | Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity |
| title_short | Recognition of yeast β-glucan particles triggers immunometabolic signaling required for trained immunity |
| title_sort | recognition of yeast β glucan particles triggers immunometabolic signaling required for trained immunity |
| topic | Physiology Molecular biology Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224002517 |
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