Περίληψη:
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 naive, 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. beta-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.
Συγγραφείς:
Saeed, Sadia
Quintin, Jessica
Kerstens, Hindrik H. D.
Rao,
Nagesha A.
Aghajanirefah, Ali
Matarese, Filomena
Cheng,
Shih-Chin
Ratter, Jacqueline
Berentsen, Kim
van der Ent,
Martijn A.
Sharifi, Nilofar
Janssen-Megens, Eva M.
Ter
Huurne, Menno
Mandoli, Amit
van Schaik, Tom
Ng, Aylwin and
Burden, Frances
Downes, Kate
Frontini, Mattia
Kumar, Vinod
and Giamarellos-Bourboulis, Evangelos J.
Ouwehand, Willem H.
van
der Meer, Jos W. M.
Joosten, Leo A. B.
Wijmenga, Cisca and
Martens, Joost H. A.
Xavier, Ramnik J.
Logie, Colin
Netea,
Mihai G.
Stunnenberg, Hendrik G.
