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

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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:42

Enthalten in:

Cell reports - 42(2023), 5 vom: 30. Mai, Seite 112487

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

82115-62-6
BCG
BCG Vaccine
CP: Immunology
IFN-γ
In vivo training
Interferon-gamma
Journal Article
Monocyte heterogeneity
Research Support, Non-U.S. Gov't
STAT1
Single-cell RNA-seq
Trained immunity

Anmerkungen:

Date Completed 05.06.2023

Date Revised 08.06.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.celrep.2023.112487

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356584631