Scientific Publications

Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes.

Publication TypeJournal Article
AuthorsKleinnijenhuis, 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., and Netea MG
AbstractAdaptive 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.
Year of Publication2012
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue43
Pages17537-42
Date Published (YYYY/MM/DD)2012/10/23
ISSN Number0027-8424
DOI10.1073/pnas.1202870109
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/22988082?dopt=Abstract