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

Sadia Saeed, Jessica Quintin, Hindrik H.D. Kerstens, Nagesha A. Rao, Ali Aghajanirefah, Filomena Matarese, Shih Chin Cheng, Jacqueline Ratter, Kim Berentsem, Martijn A. Van Der Ent, Nilofar Sharifi, Eva M. Jamssern-Megens, Menno Ter Huurne, Amit Mandoli, Tom Van Schaik, Aylwin Ng, Frances Burden, Kale Downes, Mattia Frontini, Vinod KumarEvangelos J. Giamarellos-Bourboulis, Willem H. Ouwehand, Jos W.M. Van Der Meer, Leo A.B. Joosten, Cisca Wijmenga, Joost H.A. Martens, Ramnik J. Xavier, Colin Logie, Mihai G. Netea, Hendrik G. Stunnenberg

Research output: Contribution to journalArticlepeer-review

1137 Citations (Scopus)


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, ß-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.

Original languageEnglish
Article number1251086
Issue number6204
Publication statusPublished - 26 Sept 2014
Externally publishedYes


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