BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis
Open accessAbstract
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
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TII occurs not only in mature myeloid cells but also in immature progenitors, and thus can be long-lived.
“Studies have shown that TII occurs not only in mature myeloid cells, as previously believed, but also in immature progenitors, and thus can be long-lived [74,76].”
From Clonal hematopoiesis and inflammation – the perpetual cycle (2023) · cites this paper as [74]
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- Authors
- Kaufmann, E., Sanz, J., Dunn, J. L., Khan, N., Mendonça, L. E., Pacis, A., Tzelepis, F., Pernet, E., Dumaine, A., Grenier, J.-C., Mailhot-Léonard, F., Ahmed, E., Belle, J., Besla, R., Mazer, B., King, I. L., Nijnik, A., Robbins, C. S., Barreiro, L. B., & Divangahi, M.
- Affiliations
- McGill University Health Centre (CA)
- CHU Sainte-Justine Research Center (CA)
- McGill University (CA)
- University of Toronto (CA)
- Corresponding author
- Barreiro, Luis B.
- Divangahi, Maziar
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 172
- Issue
- 1-2
- Pages
- 176-190.e19
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2783711120
- Cited by
- 1,191
- References
- 10
- Citations by year
- 2026: 165 · 2025: 154 · 2024: 119 · 2023: 135 · 2022: 127 · 2021: 180 · 2020: 154 · 2019: 98 · 2018: 56 · 2017: 1 · 2013: 1
- FWCI
- 51.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institute of Health Research (FDN-143273, 301538, 232519)
- Fonds de Recherche du Québec-Santé
- Canada Research Chair (950-228993)
- German Research Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- BCG, hematopoietic stem cells, tuberculosis, innate immunity, bone marrow, myelopoiesis, lymphocyte development, macrophages, epigenetic modifications, multipotent progenitors, tuberculosis vaccine, monocyte/macrophage lineage
- MeSH terms
- Animals, Cell Line, Cells, Cultured, Hematopoiesis, Hematopoietic Stem Cells, Immunity, Innate, Immunologic Memory, Mice, Inbred C57BL, Mycobacterium bovis, Tuberculosis, Epigenesis, Genetic, Mice, Transcriptome
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