Interleukin-1β Induces Trained Innate Immunity in Human Hematopoietic Progenitor Cells In vitro

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2024 Nov 8

PMID 39515317

Authors

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

Affiliations

Soon will be listed here.

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.

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