BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment
Open accessAbstract
Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift. These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1 SNP variants that correlate with trained immunity, and elevated serum concentrations of the HNF1 target alpha-1 antitrypsin. Additionally, transcriptomic HSPC remodeling was epigenetically conveyed to peripheral CD14+ monocytes, displaying an activated transcriptional signature three months after BCG vaccination. Taken together, transcriptomic, epigenomic, and functional reprogramming of HSPCs and peripheral monocytes is a hallmark of BCG-induced trained immunity in humans.
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Enhanced neutrophil function has also been documented in mammals with trained immunity.
“Though much of the previous research focused on cells of the macrophage linage, our observation of enhanced neutrophil function has also been documented in mammals with trained immunity [38,39].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [38]
The Results section reports increased expression of genes involved in neutrophil development and function after BCG vaccination, and higher circulating neutrophil counts in vaccinated infants. It does not report a direct measurement of enhanced neutrophil function, so that part of the claim goes beyond the evidence in our copy. No page numbers are provided. (LLM, conf=0.85)
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Self-citationTrained innate immunity, long-lasting epigenetic modulation, and skewed myelopoiesis by heme
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Self-citationTrained immunity in atherosclerotic cardiovascular disease
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Self-citationIntravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge
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Exploring the oral-gut linkage: Interrelationship between oral and systemic diseases
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β-Glucan Induces Distinct and Protective Innate Immune Memory in Differentiated Macrophages
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Self-citationBCG vaccination provides protection against IAV but not SARS-CoV-2
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Self-citationThe role of neutrophils in trained immunity
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Trained immunity in chronic inflammatory diseases and cancer
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Self-citationB-Cells and Antibodies as Contributors to Effector Immune Responses in Tuberculosis
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Self-citationTrained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine
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- Authors
- Cirovic, B., de Bree, L. C. J., Groh, L., Blok, B. A., Chan, J., van der Velden, W. J. F. M., Bremmers, M. E. J., van Crevel, R., Händler, K., Picelli, S., Schulte-Schrepping, J., Klee, K., Oosting, M., Koeken, V. A. C. M., van Ingen, J., Li, Y., Benn, C. S., Schultze, J. L., Joosten, L. A. B., Curtis, N., Netea, M. G., & Schlitzer, A.
- Affiliations
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- Statens Serum Institut (DK)
- Royal Children's Hospital (AU)
- Radboud University Medical Center (NL)
- Corresponding author
- Netea, Mihai G.
- Schlitzer, Andreas
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 28
- Issue
- 2
- Pages
- 322-334.e5
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7295478
- OpenAlex
- W3035001102
- Cited by
- 510
- References
- 52
- Citations by year
- 2026: 85 · 2025: 90 · 2024: 72 · 2023: 82 · 2022: 74 · 2021: 70 · 2020: 36 · 2013: 1
- FWCI
- 23.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed Central (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- DZNE Pub (submittedVersion)
- HZI (Helmholtz Centre for Infection Research) (submittedVersion, cc-by-nc-sa)
- Funders
- Horizon 2020 Framework Programme
- European Research Council (833247)
- Deutsche Forschungsgemeinschaft (EXC2151 – 390873048, SCHL2116/1)
- Danmarks Grundforskningsfond (DNRF108)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Horizon 2020 (733100)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Keywords
- BCG vaccination, trained immunity, hematopoietic stem and progenitor cells, HNF1A, HNF1B, myeloid cell development, bone marrow, CD14+ monocytes, epigenetic reprogramming, alpha-1-antitrypsin, heterologous immunity, infants, transcriptional reprogramming
- MeSH terms
- alpha 1-Antitrypsin, BCG Vaccine, Bone Marrow, Bone Marrow Cells, Female, Granulocytes, Hematopoiesis, Hematopoietic Stem Cells, Humans, Male, Monocytes, Mycobacterium bovis, Transcription, Genetic, Vaccination, Cytokines, Lipopolysaccharide Receptors, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Young Adult, Transcriptome, Healthy Volunteers
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