Candida albicans Infection Affords Protection against Reinfection via Functional Reprogramming of Monocytes
Open accessAbstract
Immunological memory in vertebrates is often exclusively attributed to T and B cell function. Recently it was proposed that the enhanced and sustained innate immune responses following initial infectious exposure may also afford protection against reinfection. Testing this concept of "trained immunity," we show that mice lacking functional T and B lymphocytes are protected against reinfection with Candida albicans in a monocyte-dependent manner. C. albicans and fungal cell wall β-glucans induced functional reprogramming of monocytes, leading to enhanced cytokine production in vivo and in vitro. The training required the β-glucan receptor dectin-1 and the noncanonical Raf-1 pathway. Monocyte training by β-glucans was associated with stable changes in histone trimethylation at H3K4, which suggests the involvement of epigenetic mechanisms in this phenomenon. The functional reprogramming of monocytes, reminiscent of similar NK cell properties, supports the concept of "trained immunity" and may be employed for the design of improved vaccination strategies.
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Trained immunity in mice results from epigenetic reprogramming of monocytes and macrophages through acetylation or methylation of specific lysines in histone-H3.
“Trained immunity in mice results from epigenetic reprogramming of monocytes and macrophages through acetylation or methylation of specific lysines in the histone-H3 [8,9].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [8]
The Results (Molecular Regulation of Trained Monocytes) report increased histone-H3 lysine-4 trimethylation (H3K4me3) in macrophages from trained mice, and the Discussion links H3K4me3 changes to monocyte training. The paper does not establish that epigenetic reprogramming causes trained immunity in mice; it describes the changes as associated with training and does not report histone-H3 acetylation as a mechanism. (LLM, conf=0.86)
Experimental — accuracy not yet measuredBeta glucan exposure can induce these histone modifications in mammals via the dectin-1 receptor.
“Beta glucan exposure can induce these modifications in mammals, via the dectin-1 receptor [7,8,9].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [8]
In Results, “Molecular Regulation of Trained Monocytes” (page not provided), β-glucan treatment increased H3K4me3 in human monocytes, while H3K27me3 changed little. The Results section on the dectin-1/Raf-1 pathway shows that dectin-1 is needed for effective β-glucan training, but does not directly show that the histone changes occur through that receptor; the mouse histone experiment used C. albicans rather than β-glucan exposure. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe same modifications of histone 3 were present in immune relevant gene locations in myeloid cells of humans and mice after induction of trained immunity.
“The same modifications of histone 3 were present in immune relevant gene locations in myeloid cells of humans and mice after induction of trained immunity [8,9,40].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [8]
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- Authors
- Quintin, J., Saeed, S., Martens, J. H. A., Giamarellos-Bourboulis, E. J., Ifrim, D. C., Logie, C., Jacobs, L., Jansen, T., Kullberg, B.-J., Wijmenga, C., Joosten, L. A. B., Xavier, R. J., van der Meer, J. W. M., Stunnenberg, H. G., & Netea, M. G.
- Affiliations
- Radboud University Nijmegen (NL)
- University Medical Center Groningen (NL)
- Broad Institute (US)
- Corresponding author
- Netea, Mihai G.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 12
- Issue
- 2
- Pages
- 223-232
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3864037
- OpenAlex
- W2128337342
- Cited by
- 1,289
- References
- 41
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- FWCI
- 13.24
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- journal article
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- en
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- bronze
- doi.org
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- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- HAL (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (EU-FP7)
- 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
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- trained immunity, Candida albicans, reinfection, monocyte reprogramming, β-glucan, Dectin-1, H3K4 trimethylation, epigenetic memory, cytokine production, antifungal immunity, vaccination strategies
- MeSH terms
- Dectin-1, Animals, Candida albicans, Candidiasis, Cells, Cultured, Female, Humans, Mice, Inbred C57BL, Monocytes, Cytokines, Proto-Oncogene Proteins c-raf, Lectins, C-Type, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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