Journal
CELL REPORTS
Volume 17, Issue 10, Pages 2562-2571Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.11.011
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Funding
- ERC consolidator grant [310372]
- Northern Portugal Regional Operational Programme (NORTE), under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
- Fundacao para a Ciencia e Tecnologia (FCT) [IF/00735/2014, IF/00021/2014, SFRH/BPD/96176/2013]
- FEDER funds through COMPETE - Programa Operacional Competitividade e Internacionalizacao (POCI) [LISBOA-01-0145-FEDER-007660]
- national funds through the FCT [SFRH/BPD/111100/2015]
- FCT [RECI/BBB-BQB/0230/2012]
- ERC starting grant [310496]
- Fundação para a Ciência e a Tecnologia [RECI/BBB-BQB/0230/2012] Funding Source: FCT
- European Research Council (ERC) [310496] Funding Source: European Research Council (ERC)
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The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.
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