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.

Immunometabolic Pathways in BCG-Induced Trained Immunity / Arts, Rob J. W; Carvalho, Agostinho; LA ROCCA, Claudia; Palma, Carla; Rodrigues, Fernando; Silvestre, Ricardo; Kleinnijenhuis, Johanneke; Lachmandas, Ekta; Gonçalves, Luís G; Belinha, Ana; Cunha, Cristina; Oosting, Marije; Joosten, Leo A. B; Matarese, Giuseppe; van Crevel, Reinout; Netea, Mihai G.. - In: CELL REPORTS. - ISSN 2211-1247. - 17:10(2016), pp. 2562-2571-2571. [10.1016/j.celrep.2016.11.011]

Immunometabolic Pathways in BCG-Induced Trained Immunity

LA ROCCA, CLAUDIA;MATARESE, GIUSEPPE;
2016

Abstract

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.
2016
Immunometabolic Pathways in BCG-Induced Trained Immunity / Arts, Rob J. W; Carvalho, Agostinho; LA ROCCA, Claudia; Palma, Carla; Rodrigues, Fernando; Silvestre, Ricardo; Kleinnijenhuis, Johanneke; Lachmandas, Ekta; Gonçalves, Luís G; Belinha, Ana; Cunha, Cristina; Oosting, Marije; Joosten, Leo A. B; Matarese, Giuseppe; van Crevel, Reinout; Netea, Mihai G.. - In: CELL REPORTS. - ISSN 2211-1247. - 17:10(2016), pp. 2562-2571-2571. [10.1016/j.celrep.2016.11.011]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/670546
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