Director of Immunobiology/Associate Professor of Medicine Massachusetts General Hospital/Harvard Medical School Charlestown, Massachusetts, United States
Abstract Text: When the bacillus Calmette-Guérin (BCG) vaccine (live, avirulent Mycobacterium bovis) is introduced as experimental therapy into human hosts with underlying type 1 diabetes (T1D), the BCG bacillus gradually shifts energy metabolism in host blood lymphoid cells from oxidative phosphorylation to aerobic glycolysis, drawing more glucose out of the blood to fuel intracellular metabolism. This may underlie the BCG bacillus’ therapeutic benefit: systemic, long-term reduction of excess blood glucose in TID patients. The organ-specific niches where the BCG bacillus alters metabolism and establishes persistent residence are not known. In a human clinical trial, we mapped organ niches for the BCG-induced shift to aerobic glycolysis using fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and x-ray computed tomography (CT). This allowed us to identify organs with heightened glucose uptake in T1D participants (n=6) over a 2-year period after BCG vaccination versus prior and confirmed earlier work that BCG vaccination gradually lowers blood sugar levels without contribution from endogenous insulin. We also tested BALB/c mice (n=17) for the presence of BCG colonies in particular organ niches before and after vaccination. Results from the human and murine studies concurred that the major anatomic site of functional metabolic change and residence is the spleen. The BCG bacillus also transiently mapped to the bone marrow, liver, circulating lymphocytes in the descending aorta, and lungs. These findings support the spleen as the niche for the BCG vaccine’s functional improvement of metabolism, and it is a lymphoid organ large enough to explain BCG’s systemic benefits in T1D.
