Potentiation of the axis involving pentose phosphate pathway/NADPH oxidase/reactive oxygen species drives higher IL‐10 production in monocytes of Sub‐Saharan Africans

Abstract

AbstractCellular 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.