Bacille Calmette-Guérin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes
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Abstract
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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The record
- Venue
- Proceedings of the National Academy of Sciences
- Topic
- Immune responses and vaccinations
- Field
- Immunology and Microbiology
- Canadian institutions
- Institute of Infection and Immunity
- Funders
- National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesHigher Education Commision, PakistanNational Institutes of HealthLeona M. and Harry B. Helmsley Charitable Trust
- Keywords
- NOD2Innate immune systemImmunologyVaccinationBiologyImmunityImmune systemAcquired immune systemReprogrammingEpigeneticsCellGeneticsGene
- Has abstract in OpenAlex
- yes