TY - JOUR
T1 - Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity
AU - Saeed, Sadia
AU - Quintin, Jessica
AU - Kerstens, Hindrik H.D.
AU - Rao, Nagesha A.
AU - Aghajanirefah, Ali
AU - Matarese, Filomena
AU - Cheng, Shih Chin
AU - Ratter, Jacqueline
AU - Berentsem, Kim
AU - Van Der Ent, Martijn A.
AU - Sharifi, Nilofar
AU - Jamssern-Megens, Eva M.
AU - Ter Huurne, Menno
AU - Mandoli, Amit
AU - Van Schaik, Tom
AU - Ng, Aylwin
AU - Burden, Frances
AU - Downes, Kale
AU - Frontini, Mattia
AU - Kumar, Vinod
AU - Giamarellos-Bourboulis, Evangelos J.
AU - Ouwehand, Willem H.
AU - Van Der Meer, Jos W.M.
AU - Joosten, Leo A.B.
AU - Wijmenga, Cisca
AU - Martens, Joost H.A.
AU - Xavier, Ramnik J.
AU - Logie, Colin
AU - Netea, Mihai G.
AU - Stunnenberg, Hendrik G.
PY - 2014/9/26
Y1 - 2014/9/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907483941&partnerID=8YFLogxK
U2 - 10.1126/science.1251086
DO - 10.1126/science.1251086
M3 - Article
C2 - 25258085
AN - SCOPUS:84907483941
SN - 0036-8075
VL - 345
JO - Science
JF - Science
IS - 6204
M1 - 1251086
ER -