@article{3162982,
    title = "mTOR- and HIF-1 alpha-mediated aerobic glycolysis as metabolic basis for
trained immunity",
    author = "Cheng, Shih-Chin and Quintin, Jessica and Cramer, Robert A. and and Shepardson, Kelly M. and Saeed, Sadia and Kumar, Vinod and and Giamarellos-Bourboulis, Evangelos J. and Martens, Joost H. A. and Rao, and Nagesha Appukudige and Aghajanirefah, Ali and Manjeri, Ganesh R. and Li, and Yang and Ifrim, Daniela C. and Arts, Rob J. W. and van der Meer, Brian and M. J. W. and Deen, Peter M. T. and Logie, Colin and O'Neill, Luke A. and and Willems, Peter and van de Veerdonk, Frank L. and van der Meer, Jos W. M. and and Ng, Aylwin and Joosten, Leo A. B. and Wijmenga, Cisca and and Stunnenberg, Hendrik G. and Xavier, Ramnik J. and Netea, Mihai G.",
    journal = "SCIENCE CHINA Information Sciences",
    year = "2014",
    volume = "345",
    number = "6204",
    pages = "1579+",
    publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
    doi = "10.1126/science.1250684",
    abstract = "Epigenetic reprogramming of myeloid cells, also known as trained
immunity, confers nonspecific protection from secondary infections.
Using histone modification profiles of human monocytes trained with the
Candida albicans cell wall constituent beta-glucan, together with a
genome-wide transcriptome, we identified the induced expression of genes
involved in glucose metabolism. Trained monocytes display high glucose
consumption, high lactate production, and a high ratio of nicotinamide
adenine dinucleotide (NAD+) to its reduced form (NADH), reflecting a
shift in metabolism with an increase in glycolysis dependent on the
activation of mammalian target of rapamycin (mTOR) through a
dectin-1-Akt-HIF-1 alpha (hypoxia-inducible factor-1 alpha) pathway.
Inhibition of Akt, mTOR, or HIF-1 alpha blocked monocyte induction of
trained immunity, whereas the adenosine monophosphate-activated protein
kinase activator metformin inhibited the innate immune response to
fungal infection. Mice with a myeloid cell-specific defect in HIF-1
alpha were unable to mount trained immunity against bacterial sepsis.
Our results indicate that induction of aerobic glycolysis through an
Akt-mTOR-HIF-1 alpha pathway represents the metabolic basis of trained
immunity."
}