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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\u2013independent 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.<\/jats:p>","DOI":"10.1073\/pnas.1202870109","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T01:50:32Z","timestamp":1347933032000},"page":"17537-17542","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1657,"title":["Bacille Calmette-Gu\u00e9rin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes"],"prefix":"10.1073","volume":"109","author":[{"given":"Johanneke","family":"Kleinnijenhuis","sequence":"first","affiliation":[{"name":"Department of Medicine,"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Quintin","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Preijers","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine\u2013Laboratory of Hematology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo A. B.","family":"Joosten","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela C.","family":"Ifrim","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadia","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cor","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Department of Medicine,"},{"name":"Nijmegen Institute for Infection, Inflammation and Immunity (N4i), and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joke","family":"van Loenhout","sequence":"additional","affiliation":[{"name":"Public Health Office GGD, Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik G.","family":"Stunnenberg","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Faculties of Science and Medicine, Nijmegen Centre for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramnik J.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114; and"},{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos W. 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