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A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity.

Cell reports

Authors: Wenchao Li, Simone J C F M Moorlag, Valerie A C M Koeken, Rutger J Röring, L Charlotte J de Bree, Vera P Mourits, Manoj K Gupta, Bowen Zhang, Jianbo Fu, Zhenhua Zhang, Inge Grondman, Krista E van Meijgaarden, Liang Zhou, Ahmed Alaswad, Leo A B Joosten, Reinout van Crevel, Cheng-Jian Xu, Mihai G Netea, Yang Li

Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8 T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 37155329

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