Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro
Innate immune cells can develop a long-lasting hyperresponsive phenotype, termed trained immunity, mediated by epigenetic and metabolic reprogramming. In mice, exposure to Bacille Calmette-Guérin (BCG), β-glucan, or Western diet induces trained immunity by reprogramming hematopoietic progenitor cells (HPCs), through interleukin-1β (IL-1β) signaling in the bone marrow (BM). We investigated whether IL-1β induces trained immunity in primary human BM-derived HPCs in vitro. We exposed human BM-derived HPCs to IL-1β for 4 h. HPCs were expanded and differentiated into monocytes followed by functional and transcriptomic characterization. IL-1β-exposed HPCs showed higher granulocyte-macrophage colony-forming units. The monocyte offspring produced more tumor necrosis factor (TNF) and IL-1β after restimulation with lipopolysaccharide (LPS) and Pam3Cys and is metabolically more active. Transcriptomic analysis showed upregulation of key atherogenic and inflammatory pathways. In conclusion, brief exposure of human BM-derived HPCs to IL-1β in vitro induces a trained immunity phenotype.
Authors
- Nicolaas PM Schaap (ORCID: https://orcid.org/0000-0001-7696-4752)
- Boris Novakovic (ORCID: https://orcid.org/0000-0002-5623-9008)
- Mihai Gheorghe Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
- Daniela Flores-Gomez (ORCID: https://orcid.org/0000-0003-0443-0107)
- Siroon Bekkering (ORCID: https://orcid.org/0000-0003-1149-466X)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Diede van Ens (ORCID: https://orcid.org/0000-0001-7273-4896)
- Niels Peter Riksen (ORCID: https://orcid.org/0000-0001-9197-8124)
- Wim H. C. Rijnen (ORCID: https://orcid.org/0000-0002-7383-8053)
- Elise L. Kessler (ORCID: https://orcid.org/0000-0003-1974-4571)
- Willemijn Hobo (ORCID: https://orcid.org/0000-0002-8206-8185)
Institutions
- Royal Children's Hospital (AU)
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- The University of Melbourne (AU)
- Iuliu Hațieganu University of Medicine and Pharmacy (RO)
- University Medical Center (US)
- Radboud University Medical Center (NL)
- University Medical Center Utrecht (NL)
- Radboud Institute for Molecular Life Sciences (NL)
- Murdoch Children's Research Institute (AU)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1016/j.stemcr.2024.09.004
- Citations
- 20
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 4.81
Funders
- Dutch Cardiovascular Alliance
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- European Research Area Network on Cardiovascular Diseases
- National Institutes of Health
- National Health and Medical Research Council
- Netherlands Heart Institute
- National Heart, Lung, and Blood Institute