Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 558616
Title Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity
Author(s) Arts, Rob J.W.; Novakovic, Boris; Horst, Rob ter; Carvalho, Agostinho; Bekkering, Siroon; Lachmandas, Ekta; Rodrigues, Fernando; Silvestre, Ricardo; Cheng, Shih Chin; Wang, Shuang Yin; Habibi, Ehsan; Gonçalves, Luís G.; Mesquita, Inês; Cunha, Cristina; Laarhoven, Arjan van; Veerdonk, Frank L. van de; Williams, David L.; Meer, Jos W.M. van der; Logie, Colin; O'Neill, Luke A.; Dinarello, Charles A.; Riksen, Niels P.; Crevel, Reinout van; Clish, Clary; Notebaart, Richard A.; Joosten, Leo A.B.; Stunnenberg, Hendrik G.; Xavier, Ramnik J.; Netea, Mihai G.
Source Cell Metabolism 24 (2016)6. - ISSN 1550-4131 - p. 807 - 819.
DOI https://doi.org/10.1016/j.cmet.2016.10.008
Publication type Refereed Article in a scientific journal
Publication year 2016
Keyword(s) cholesterol metabolism - epigenetics - glutamine metabolism - glycolysis - trained immunity
Abstract

Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to β-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.

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