Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes.

Adult BCG Vaccine / genetics Cytokines / immunology Female Gene Expression / genetics Gene Expression Profiling / methods Gene Expression Regulation / genetics Healthy Volunteers Humans Immunity / genetics Immunity, Innate / drug effects Immunologic Memory / immunology Inflammation Inflammation Mediators / pharmacology Male Monocytes / immunology Transcriptome / genetics Vaccination
BCG vaccination cytokines humanin monocytes non-specific effects of vaccines single-cell sequencing trained immunity

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
16 11 2021
Historique:
received: 21 12 2020
revised: 31 08 2021
accepted: 29 10 2021
entrez: 17 11 2021
pubmed: 18 11 2021
medline: 15 2 2022
Statut: ppublish

Résumé

Bacillus Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines worldwide. In addition to protection against tuberculosis, BCG confers a degree of non-specific protection against other infections by enhancing secondary immune responses to heterologous pathogens, termed "trained immunity." To better understand BCG-induced immune reprogramming, we perform single-cell transcriptomic measurements before and after BCG vaccination using secondary immune stimulation with bacterial lipopolysaccharide (LPS). We find that BCG reduces systemic inflammation and identify 75 genes with altered LPS responses, including inflammatory mediators such as CCL3 and CCL4 that have a heightened response. Co-expression analysis reveals that gene modules containing these cytokines lose coordination after BCG. Other modules exhibit increased coordination, including several humanin nuclear isoforms that we confirm induce trained immunity in vitro. Our results link in vivo BCG administration to single-cell transcriptomic changes, validated in human genetics experiments, and highlight genes that are putatively responsible for non-specific protective effects of BCG.

Identifiants

DOI: 10.1016/j.celrep.2021.110028 PMID: 34788625 PMC: PMC8728743
pubmed: 34788625
pii: S2211-1247(21)01510-2
doi: 10.1016/j.celrep.2021.110028
pmc: PMC8728743
mid: NIHMS1757902
pii:
doi:

Substances chimiques

BCG Vaccine 0
Cytokines 0
Inflammation Mediators 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

110028

Subventions

Organisme : European Research Council
ID : 833247
Pays : International
Organisme : NIDDK NIH HHS
ID : RC2 DK114784
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests R.J.X. is co-founder of Celsius Therapeutics and Jnana Therapeutics. M.G.N. and L.A.B.J. are scientific founders of Trained Therapeutix and Discovery (TTxD).

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Auteurs

Lingjia Kong (L)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Simone J C F M Moorlag (SJCFM)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.

Ariel Lefkovith (A)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Bihua Li (B)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Vasiliki Matzaraki (V)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.

Liesbeth van Emst (L)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.

Heather A Kang (HA)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Isabel Latorre (I)

Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Martin Jaeger (M)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.

Leo A B Joosten (LAB)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca 400000, Romania.

Mihai G Netea (MG)

Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany. Electronic address: mihai.netea@radboudumc.nl.

Ramnik J Xavier (RJ)

Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: xavier@molbio.mgh.harvard.edu.

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