ArticleGenome biology2025
Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.
Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Trained Immunity Induced by Vaccines: A Shifting Paradigm for Infant and Adult Immunity.International journal of molecular sciences · 2026Review
- Bacillus Calmette-Guérin (BCG) Vaccination and the Immune-Brain Axis: Implications for Neuroprotection and Neurodegenerative Disease.Vaccines · 2026Review
- Tissue context as a determinant of trained innate immunity: a conserved molecular toolkit with divergent functional outputs.Journal of leukocyte biology · 2026Review
- How to Employ Trained Immunity and Trained Immunity-Based Vaccines to Inhibit Allergic Inflammation.Vaccines · 2026Review
- The potential role of trained immunity in HIV-associated atherosclerotic cardiovascular disease: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.Genome biology · 2025Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
backgroundEpigenetic reprogramming shapes immune memory in both innate (trained immunity) and adaptive immune cells following Bacillus Calmette-Guérin (BCG) vaccination. However, the role of dynamic DNA methylation changes in post-vaccination immune responses remains unclear.
resultsWe established a cohort of 284 healthy Dutch individuals, profiling genome-wide DNA methylation and cytokine responses to ex vivo stimulation at baseline, 14 days, and 90 days post-BCG vaccination. We identified distinct patterns of DNA methylation alternations in the short- and long-term following BCG vaccination. Moreover, we established that baseline DNA methylation profiles exert influence on the change in interferon-γ (IFN-γ) production upon heterologous (Staphylococcus aureus) stimulation before and after BCG vaccination. Specifically, we identified the regulation of kisspeptin as a novel pathway implicated in the modulation of IFN-γ production, and this finding has been substantiated through experimental validation. We also observed associations between BCG-induced DNA methylation changes and increased IFN-γ and interleukin-1 β (IL-1β) production upon S. aureus stimulation. Interestingly, by integrating with genetic, epigenetic, and cytokine response data from the same individuals, mediation analysis demonstrated that most of the identified DNA methylation changes played a mediating role between genetic variants and cytokine responses; for example, the changes of cg21375332 near SLC12 A3 gene mediated the regulation of genetic variants on IFN-γ changes after BCG vaccination. Sex-specific effects were observed in DNA methylation and cytokine responses, highlighting the importance of considering sex in immune studies.
conclusionsThese findings provide deeper insights into immune response mechanisms, crucial for developing effective epigenetic-based medical interventions for personalized medicine.
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