The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes
Open accessAbstract
Adaptive features of innate immunity, recently described as “trained immunity,” have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guérin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of circulating monocytes persisted for at least 3 mo after vaccination and was accompanied by increased expression of activation markers such as CD11b and Toll-like receptor 4. These training effects were induced through the NOD2 receptor and mediated by increased histone 3 lysine 4 trimethylation. In experimental studies, BCG vaccination induced T- and B-lymphocyte–independent protection of severe combined immunodeficiency SCID mice from disseminated candidiasis (100% survival in BCG-vaccinated mice vs. 30% in control mice). In conclusion, BCG induces trained immunity and nonspecific protection from infections through epigenetic reprogramming of innate immune cells.
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“our findings corroborate a wealth of emerging evidence that NOD2 stimulation by MDP and its analogs can alter host immunity through multiple pathways including the direct activation of macrophages for tumor cell clearance (39), epigenetic reprogramming of monocytes (40, 41), generation of conventional type 1 dendritic cells (42), and priming of dendritic cells for cross-presentation to CD8+ T cell”
From Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy (2021) · cites this paper as [40]
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Citations
Cites
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Durrant, W. E., & Dong, X. (2004) · Annual Review of Phytopathology · doi:10.1146/annurev.phyto.42.040803.140421 · Cited by 3,184
Trained Immunity: A Memory for Innate Host Defense
Netea, M. G., Quintin, J., & van der Meer, J. W. M. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.006 · Cited by 1,760
Self-citationAdaptive Immune Features of Natural Killer Cells
Sun, J. C., Beilke, J., & Lanier, L. (2009) · Nature · doi:10.1038/nature07665 · Cited by 1,647
Variation in protection by BCG: implications of and for heterologous immunity
Fine, P. (1995) · The Lancet · doi:10.1016/s0140-6736(95)92348-9 · Cited by 1,385
Sylvester, R. J., van der Meijden, A. P. M., & Lamm, D. L. (2002) · The Journal of Urology · doi:10.1016/s0022-5347(05)64273-5 · Cited by 1,319
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T cell– and B cell–independent adaptive immunity mediated by natural killer cells
O’Leary, J. G., Goodarzi, M., Drayton, D. L., & von Andrian, U. H. (2006) · Nature Immunology · doi:10.1038/ni1332 · Cited by 920
REGULATION OF TH2 DIFFERENTIATION AND Il4 LOCUS ACCESSIBILITY
Ansel, K. M., Djuretic, I. M., Tanasă, B., & Rao, A. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115821 · Cited by 652
Aaby, P., Roth, A., Ravn, H., Napirna, B. M., Rodrigues, A., Lisse, I. M., Stensballe, L. G., Diness, B. R., Lausch, K. R., Lund, N., et al. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir240 · Cited by 581
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Trained immunity: A program of innate immune memory in health and– disease
Netea, M. G., Joosten, L. A. B., Latz, E., Mills, K. H. G., Natoli, G., Stunnenberg, H. G., O’Neill, L. A. J., & Xavier, R. J. (2016) · Science · doi:10.1126/science.aaf1098 · Cited by 2,768
“BCG vaccination has also been shown to result in an increase in inflammatory mediators produced by monocytes from healthy volunteers, which correlated with parallel changes in a histone modification associated with gene activation (37).”
BackgroundMethodSelf-citationDefining trained immunity and its role in health and disease
Netea, M. G., Domínguez-Andrés, J., Barreiro, L. B., Chavakis, T., Divangahi, M., Fuchs, E., Joosten, L. A. B., van der Meer, J. W. M., Mhlanga, M. M., Mulder, W. J. M., et al. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0285-6 · Cited by 2,690
Self-citationToll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity
Cheng, S.-C., Quintin, J., Cramer, R. A., Shepardson, K. M., Saeed, S., Kumar, V., Giamarellos-Bourboulis, E. J., Martens, J. H. A., Rao, N. A., Aghajanirefah, A., et al. (2014) · Science · doi:10.1126/science.1250684 · Cited by 2,224
“In line with the proposal that there are nonspecific adaptive responses in the innate immune system, T and B cell–independent protective effects of monocytes and natural killer (NK) cells have been demonstrated in models of bacterial and viral infections, respectively (5, 6).”
InfluentialSelf-citationMicroglial M1/M2 polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070
“, 2011) and a lymphocyte-independent shaping of innate immunity has been termed ‘memory’ (Kurtz and Franz, 2003; Kleinnijenhuis et al., 2012).”
Background
Metadata
- Authors
- Kleinnijenhuis, J., Quintin, J., Preijers, F., Joosten, L. A. B., Ifrim, D. C., Saeed, S., Jacobs, C., van Loenhout, J., de Jong, D., Stunnenberg, H. G., Xavier, R. J., van der Meer, J. W. M., van Crevel, R., & Netea, M. G.
- Affiliations
- Radboud University Medical Center (NL)
- Department of Medicine,
- Radboud University Nijmegen (NL)
- Public Health Office GGD, Nijmegen, The Netherlands;
- Department of Gastroenterology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands;
- Broad Institute (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-09-17
- Volume
- 109
- Issue
- 43
- Pages
- 17537-17542
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3491454
- OpenAlex
- W2059403792
- Cited by
- 1,728
- References
- 35
- Citations by year
- 2026: 139 · 2025: 174 · 2024: 127 · 2023: 150 · 2022: 170 · 2021: 226 · 2020: 204 · 2019: 118 · 2018: 119 · 2017: 79 · 2016: 74 · 2015: 68 · 2014: 51 · 2013: 25 · 2012: 2
- FWCI
- 20.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- HAL (submittedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Higher Education Commision, Pakistan
- National Institutes of Health (DK 043351)
- National Institute of Allergy and Infectious Diseases (AI 062773, R01AI062773)
- National Institute of Diabetes and Digestive and Kidney Diseases ((DK043351, R01DK083756, DK 83756, P30DK043351)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- BCG vaccine, trained immunity, NOD2, epigenetic reprogramming, histone H3 lysine 4 trimethylation, monocytes, innate immunity, interferon-gamma, TNF-α, IL-1β, TLR4, CD11b, candidiasis, BCG vaccination, SCID mice
- MeSH terms
- Adult, B-Lymphocytes, Base Sequence, BCG Vaccine, Histones, Humans, Methylation, Monocytes, T-Lymphocytes, Polymerase Chain Reaction, DNA Primers, Epigenesis, Genetic, Chromatin Immunoprecipitation, Nod2 Signaling Adaptor Protein
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