Shih-Chin Cheng, Jessica Quintin, Robert A Cramer, Kelly M Shepardson, Sadia Saeed, Vinod Kumar, Evangelos J Giamarellos-Bourboulis, Joost H A Martens, Nagesha Appukudige Rao, Ali Aghajanirefah, Ganesh R Manjeri, Yang Li, Daniela C Ifrim, Rob J W Arts, Brian M J W van der Veer, Peter M T Deen, Colin Logie, Luke A O'Neill, Peter Willems, Frank L van de Veerdonk, Jos W M van der Meer, Aylwin Ng, Leo A B Joosten, Cisca Wijmenga, Hendrik G Stunnenberg, Ramnik J Xavier, Mihai G Netea
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 β-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-1α (hypoxia-inducible factor-1α) pathway...
September 26, 2014: Science