Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro

Daniela Flores Gomez; Willemijn Hobo; Diede van Ens; Elise L. Kessler; Boris Novakovic; Nicolaas P M Schaap; Wim H. C. Rijnen; Leo A. B. Joosten; Mihai G Netea; Niels P Riksen; Siroon Bekkering

doi:10.1016/j.stemcr.2024.09.004

Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro

Daniela Flores Gomez
, Willemijn Hobo
, Diede van Ens
, Elise L. Kessler
, Boris Novakovic
, Nicolaas P M Schaap
, Wim H. C. Rijnen
, Leo A. B. Joosten
, Mihai G Netea
, Niels P Riksen^*
, Siroon Bekkering

^*Corresponding author for this work

Radboud University Medical Center
Murdoch Children's Research Institute
Radboud University Nijmegen
Nijmegen Institute for Infection

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1651-1664
Number of pages	14
Journal	Stem Cell Reports
Volume	19
Issue number	12
Early online date	7 Nov 2024
DOIs	https://doi.org/10.1016/j.stemcr.2024.09.004
Publication status	Published - 10 Dec 2024
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)

Funding

We would like to thank Daniek Kapteijn for helping with IBIDI experiments and Benjamin Cossins for helping with the quantification of the phagocytosis assay. L.A.B.J., M.G.N., and N.P.R. were supported by a CVON grant from the Dutch Heart Foundation and Dutch Cardiovascular Alliance (CVON2018-27). N.P.R. was further supported by a grant of the ERA-CVD Joint Transnational Call 2018, which is supported by the Dutch Heart Foundation in the Hague (JTC2018, project MEMORY; 2018T093). N.P.R. and M.G.N. were supported by a Project Program Grant of the NHLBI (Project 15-0893 and NIH/NHLBI P01HL131478). S.B. was supported by the Dutch Heart Foundation in the Hague (Dekker grant 2018-T028). M.G.N. was supported by a European Research Council (ERC) Advanced Grant (FP/2007-2013/ERC grant 2012-322698) and a Spinoza Prize (NWO SPI 92-266). E.L.K. was supported by the Netherlands Heart Institute (Fellowship #282) and E.L.K. and N.P.R. by the Netherlands Heart Institute (IMPRESS). B.N. is supported by an NHMRC (Australia) Investigator Grant (GNT1173314). The figures were created with BioRender.com.

Funders	Funder number
IMPRESS
Hartstichting
CVON
Netherlands Heart Institute	282
Dutch Cardiovascular Alliance	CVON2018-27
Dutch Heart Foundation in the Hague	2018T093, JTC2018
National Health and Medical Research Council	GNT1173314
National Heart, Lung, and Blood Institute	15-0893
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	SPI 92-266
European Research Council	FP/2007-2013/ERC, 2012-322698
National Institutes of Health	P01HL131478, 2018-T028

Keywords

bone marrow
hematopoietic progenitor cells
macrophages
monocytes
trained immunity

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10.1016/j.stemcr.2024.09.004Licence: CC BY

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title = "Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro",

abstract = "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-Gu{\'e}rin (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.",

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author = "\{Flores Gomez\}, Daniela and Willemijn Hobo and \{van Ens\}, Diede and Kessler, \{Elise L.\} and Boris Novakovic and Schaap, \{Nicolaas P M\} and Rijnen, \{Wim H. C.\} and Joosten, \{Leo A. B.\} and Netea, \{Mihai G\} and Riksen, \{Niels P\} and Siroon Bekkering",

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doi = "10.1016/j.stemcr.2024.09.004",

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T1 - Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro

AU - Flores Gomez, Daniela

AU - Hobo, Willemijn

AU - van Ens, Diede

AU - Kessler, Elise L.

AU - Novakovic, Boris

AU - Schaap, Nicolaas P M

AU - Rijnen, Wim H. C.

AU - Joosten, Leo A. B.

AU - Netea, Mihai G

AU - Riksen, Niels P

AU - Bekkering, Siroon

PY - 2024/12/10

Y1 - 2024/12/10

N2 - 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.

AB - 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.

KW - bone marrow

KW - hematopoietic progenitor cells

KW - macrophages

KW - monocytes

KW - trained immunity

UR - https://www.scopus.com/pages/publications/85210904049

U2 - 10.1016/j.stemcr.2024.09.004

DO - 10.1016/j.stemcr.2024.09.004

M3 - Article

SN - 2213-6711

VL - 19

SP - 1651

EP - 1664

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 12

ER -

Interleukin-1β induces trained innate immunity in human hematopoietic progenitor cells in vitro

Abstract

Bibliographical note

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Keywords

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