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. 2024 Sep;54(9):e2451029.
doi: 10.1002/eji.202451029. Epub 2024 Jun 14.

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

Madeleine Eunice Betouke Ongwe  1   2   3 , Yoanne D Mouwenda  1   2 , Mikhael D Manurung  1 , Graham Heieis  1 , Shohreh Azimi  1 , Ayola A Adegnika  1   2   4   5 , Peter G Kremsner  2   4 , Taco W Kuijpers  6   7 , Maria Yazdanbakhsh  1 , Bart Everts  1
Affiliations
Free article

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

Madeleine Eunice Betouke Ongwe et al. Eur J Immunol. 2024 Sep.
Free article

Abstract

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.

Keywords: IL‐10; Monocytes; NADPH‐oxidase; Pentose phosphate pathway; ROS.

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