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

Sadia Saeed (1) , Jessica Quintin (2) , Hindrik Kerstens (1) , Nagesha Rao (1) , Ali Aghajanirefah (1) , Filomena Matarese (1) , Shih-Chin Cheng (2) , Jacqueline Ratter (2) , Kim Berentsen (1) , Martijn van Der Ent (1) , Nilofar Sharifi (1) , Eva Janssen-Megens (1) , Menno ter Huurne (1) , Amit Mandoli (1) , Tom van Schaik (1) , Aylwin Ng (3, 4) , Frances Burden (5) , Kate Downes (5) , Mattia Frontini (5) , Vinod Kumar (6) , Evangelos Giamarellos-Bourboulis (7) , Willem H. Ouwehand (5) , Jos W. M. van Der Meer (2) , Leo Joosten (2) , Cisca Wijmenga (6) , Joost Martens (1) , Ramnik Xavier (8, 2) , Colin Logie (1) , Mihai G. Netea (2) , Hendrik G. Stunnenberg (1)

1 Radboud University [Nijmegen]
2 Radboud University Medical Center [Nijmegen]
3 Massachusetts General Hospital [Boston]
4 BROAD INSTITUTE - Broad Institute of MIT and Harvard
5 CAM - University of Cambridge [UK]
6 University of Groningen [Groningen]
7 NKUA - National and Kapodistrian University of Athens
8 MIT - Massachusetts Institute of Technology

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.

Domaines: Sciences du Vivant [q-bio]; Immunologie; Immunité innée

Sadia Saeed, Jessica Quintin, Hindrik Kerstens, Nagesha Rao, Ali Aghajanirefah, et al.. Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity. Science, 2014, 345 (6204), pp.1251086. ⟨10.1126/science.1251086⟩. ⟨pasteur-02875420⟩