| Literature DB >> 25258085 |
Sadia Saeed1, Jessica Quintin2, Hindrik H D Kerstens1, Nagesha A Rao1, Ali Aghajanirefah1, Filomena Matarese1, Shih-Chin Cheng2, Jacqueline Ratter2, Kim Berentsen1, Martijn A van der Ent1, Nilofar Sharifi1, Eva M Janssen-Megens1, Menno Ter Huurne1, Amit Mandoli1, Tom van Schaik1, Aylwin Ng3, Frances Burden4, Kate Downes4, Mattia Frontini4, Vinod Kumar5, Evangelos J Giamarellos-Bourboulis6, Willem H Ouwehand4, Jos W M van der Meer2, Leo A B Joosten2, Cisca Wijmenga5, Joost H A Martens1, Ramnik J Xavier3, Colin Logie7, Mihai G Netea8, Hendrik G Stunnenberg7.
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.Entities:
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Year: 2014 PMID： 25258085 PMCID： PMC4242194 DOI： 10.1126/science.1251086
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728