Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes
SourceProceedings of the National Academy of Sciences USA, 109, 43, (2012), pp. 17537-17542
Article / Letter to editor
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Laboratory of Hematology
Proceedings of the National Academy of Sciences USA
SubjectIGMD 2: Molecular gastro-enterology and hepatology N4i 1: Pathogenesis and modulation of inflammation; Molecular Biology; N4i 1: Pathogenesis and modulation of inflammation; N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; N4i 3: Poverty-related infectious diseases NCEBP 13: Infectious diseases and international health; ONCOL 3: Translational research
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-Guerin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-gamma, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1beta, 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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