BCG Vaccinations Upregulate Myc, a Central Switch for Improved Glucose Metabolism in Diabetes
Willem M. Kühtreiber,
Hiroyuki Takahashi,
Ryan C. Keefe,
Yaerin Song,
Lisa Tran,
Trevor G. Luck,
Gabriella Shpilsky,
Louisa Moore,
Sarah M. Sinton,
Jessica C. Graham,
Denise L. Faustman
Affiliations
Willem M. Kühtreiber
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Hiroyuki Takahashi
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Ryan C. Keefe
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Yaerin Song
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Lisa Tran
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Trevor G. Luck
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Gabriella Shpilsky
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Louisa Moore
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Sarah M. Sinton
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Jessica C. Graham
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA
Denise L. Faustman
Immunobiology Laboratories, Harvard Medical School & Massachusetts General Hospital, Building 149, 13th Street, Rm 3602, Boston, MA 02116, USA; Corresponding author
Summary: Myc has emerged as a pivotal transcription factor for four metabolic pathways: aerobic glycolysis, glutaminolysis, polyamine synthesis, and HIF-1α/mTOR. Each of these pathways accelerates the utilization of sugar. The BCG vaccine, a derivative of Mycobacteria-bovis, has been shown to trigger a long-term correction of blood sugar levels to near normal in type 1 diabetics (T1D). Here we reveal the underlying mechanisms behind this beneficial microbe-host interaction. We show that baseline glucose transport is deficient in T1D monocytes but is improved by BCG in vitro and in vivo. We then show, using RNAseq in monocytes and CD4 T cells, that BCG treatment over 56 weeks in humans is associated with upregulation of Myc and activation of nearly two dozen Myc-target genes underlying the four metabolic pathways. This is the first documentation of BCG induction of Myc and its association with systemic blood sugar control in a chronic disease like diabetes.
