Immunometabolic Pathways in BCG-Induced Trained Immunity

Cell Rep. 2016 Dec 6;17(10):2562-2571. doi: 10.1016/j.celrep.2016.11.011.


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.

Keywords: BCG; epigenetics; glycolysis; immunometabolism; monocytes; trained immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / immunology*
  • Chromatin Assembly and Disassembly / genetics
  • Chromatin Assembly and Disassembly / immunology
  • Epigenesis, Genetic / immunology
  • Glycolysis / immunology
  • Histone Code / genetics
  • Humans
  • Immunity, Innate*
  • Immunologic Memory / genetics*
  • Mice
  • Monocytes / immunology
  • Tuberculosis / immunology*
  • Tuberculosis / microbiology
  • Tuberculosis / prevention & control


  • BCG Vaccine