Evidence map›Paper›PMID 34788625›Full record

ArticleCell reports2021

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

Lingjia Kong, Simone J C F M Moorlag, Ariel Lefkovith, Bihua Li, Vasiliki Matzaraki, Liesbeth van Emst, Heather A Kang, Isabel Latorre, Martin Jaeger, Leo A B Joosten and 2 more

Abstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. The BCGMethodsX · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Advances in Single-Cell Sequencing for Infectious Diseases: Progress and Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Innate Immune Memory is Stimulus Specific.bioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Progress of single-cell sequencing technology in immunotherapy for tuberculosis.Frontiers in cellular and infection microbiology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Lingjia KongBroad 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 MoorlagDepartment 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 LefkovithBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bihua LiBroad 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 MatzarakiDepartment of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Liesbeth van EmstDepartment 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 KangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Isabel LatorreCenter for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Martin JaegerDepartment of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Leo A B JoostenDepartment 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 NeteaDepartment 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 XavierBroad 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.

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Systematic dissection of gut cellular circuits [at single cell resolution]RC2DK114784 · NIDDK · BROAD INSTITUTE, INC. · PI ASHENBERG, ORR, GRAHAM, DANIEL BARTHOLOMEW · 2017 to 2021
$9.0M
European Research Council 833247NIDDK NIH HHS P30 DK043351NIDDK NIH HHS RC2 DK114784
6 · The paper itself

Abstract

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.

Indexed as

AdultBCG VaccineCytokinesFemaleGene ExpressionGene Expression ProfilingGene Expression RegulationHealthy VolunteersHumansImmunityImmunity, InnateImmunologic MemoryInflammationInflammation MediatorsMaleMonocytesBCG VaccineCytokinesInflammation MediatorsBCG vaccinationcytokineshumaninmonocytesnon-specific effects of vaccinessingle-cell sequencingtrained immunity

Identifiers

PMID34788625
PMCPMC8728743

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.