|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Kleinnijenhuis, J, Quintin, J, Preijers, F, Joosten, LA, Ifrim, DC, Saeed, S, Jacobs, C, van Loenhout, J, de Jong, D, Stunnenberg, HG, Xavier, RJ, van der Meer, JW, van Crevel, R, Netea, MG|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
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.