Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth

Greta Ehlers, Annika Marie Tödtmann, Lisa Holsten, Maike Willers, Julia Heckmann, Jennifer Schöning, Maximilian Richter, Anna Sophie Heinemann, Sabine Pirr, Alexander Heinz, Christian Dopfer, Kristian Händler, Matthias Becker, Johanna Büchel, Achim Wöckel, Constantin Kaisenberg, Gesine Hansen, Karsten Hiller, Joachim L. Schultze, Christoph Härtel, Wolfgang Kastenmüller, Martin Vaeth, Thomas Ulas and Dorothee Viemann ()
Additional contact information
Greta Ehlers: Hannover Medical School
Annika Marie Tödtmann: Hannover Medical School
Lisa Holsten: University Hospital Würzburg
Maike Willers: Hannover Medical School
Julia Heckmann: University Hospital Würzburg
Jennifer Schöning: University Hospital Würzburg
Maximilian Richter: University Hospital Würzburg
Anna Sophie Heinemann: Hannover Medical School
Sabine Pirr: Hannover Medical School
Alexander Heinz: Technical University Braunschweig
Christian Dopfer: Hannover Medical School
Kristian Händler: German Center for Neurodegenerative Diseases (DZNE)
Matthias Becker: German Center for Neurodegenerative Diseases (DZNE)
Johanna Büchel: University Hospital Würzburg
Achim Wöckel: University Hospital Würzburg
Constantin Kaisenberg: Hannover Medical School
Gesine Hansen: Hannover Medical School
Karsten Hiller: Technical University Braunschweig
Joachim L. Schultze: University of Bonn
Christoph Härtel: University Hospital Würzburg
Wolfgang Kastenmüller: Julius-Maximilians-University Würzburg
Martin Vaeth: Julius-Maximilians-University Würzburg
Thomas Ulas: University of Bonn
Dorothee Viemann: Hannover Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Neonates primarily rely on innate immune defense, yet their inflammatory responses are usually restricted compared to adults. This is controversially interpreted as a sign of immaturity or essential programming, increasing or decreasing the risk of sepsis, respectively. Here, combined transcriptomic, metabolic, and immunological studies in monocytes of healthy individuals reveal an inverse ontogenetic shift in metabolic pathway activities with increasing age. Neonatal monocytes are characterized by enhanced oxidative phosphorylation supporting ongoing myeloid differentiation. This phenotype is gradually replaced during early childhood by increasing glycolytic activity fueling the inflammatory responsiveness. Microbial stimulation shifts neonatal monocytes to an adult-like metabolism, whereas ketogenic diet in adults mimicking neonatal ketosis cannot revive a neonate-like metabolism. Our findings disclose hallmarks of innate immunometabolism during healthy postnatal immune adaptation and suggest that premature activation of glycolysis in neonates might increase their risk of sepsis by impairing myeloid differentiation and promoting hyperinflammation.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57357-w

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DOI: 10.1038/s41467-025-57357-w

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