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Science. 2014 Sep 26;345(6204):1251086. doi: 10.1126/science.1251086.

Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity.

Author information

1
Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.
2
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
3
Center for Computational and Integrative Biology and Gastrointestinal Unit, Massachusetts General Hospital, Harvard School of Medicine, Boston, MA 02114, USA. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
4
Department of Haematology, University of Cambridge, Cambridge, UK. National Health Service, Blood and Transplant Cambridge Centre, Cambridge Biomedical Campus, Cambridge CB0 2PT, UK.
5
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
6
Fourth Department of Internal Medicine, University of Athens, Medical School, 1 Rimini Street, 12462 Athens, Greece.
7
Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands. h.stunnenberg@ncmls.ru.nl mihai.netea@radboudumc.nl c.logie@ncmls.ru.nl.
8
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. h.stunnenberg@ncmls.ru.nl mihai.netea@radboudumc.nl c.logie@ncmls.ru.nl.

Abstract

Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans.

Comment in

PMID:
25258085
PMCID:
PMC4242194
DOI:
10.1126/science.1251086
[Indexed for MEDLINE]
Free PMC Article

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