Potentiation of the Axis Involving Pentose Phosphate Pathway/NADPH Oxidase/reactive Oxygen Species Drives Higher IL-10 Production in Monocytes of Sub-Saharan Africans

Cellular metabolism is a key determinant of immune cell function. Here we found that CD14 monocytes from Sub-Saharan Africans produce higher levels of IL-10 following TLR-4 stimulation and are bioenergetically distinct from monocytes from Europeans. Through metabolomic profiling, we identified the higher IL-10 production to be driven by increased baseline production of NADPH oxidase-dependent reactive oxygen species, supported by enhanced pentose phosphate pathway activity. Together, these data indicate that NADPH oxidase-derived ROS is a metabolic checkpoint in monocytes that governs their inflammatory profile and uncovers a metabolic basis for immunological differences across geographically distinct populations.