TY  - JOUR
AU  - Ehlers, Greta
AU  - Tödtmann, Annika Marie
AU  - Holsten, Lisa
AU  - Willers, Maike
AU  - Heckmann, Julia
AU  - Schöning, Jennifer
AU  - Richter, Maximilian
AU  - Heinemann, Anna Sophie
AU  - Pirr, Sabine
AU  - Heinz, Alexander
AU  - Dopfer, Christian
AU  - Händler, Kristian
AU  - Becker, Matthias
AU  - Büchel, Johanna
AU  - Wöckel, Achim
AU  - von Kaisenberg, Constantin
AU  - Hansen, Gesine
AU  - Hiller, Karsten
AU  - Schultze, Joachim L
AU  - Härtel, Christoph
AU  - Kastenmüller, Wolfgang
AU  - Vaeth, Martin
AU  - Ulas, Thomas
AU  - Viemann, Dorothee
TI  - Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-00407
SP  - 2239
PY  - 2025
AB  - 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.
KW  - Oxidative Phosphorylation
KW  - Humans
KW  - Monocytes: immunology
KW  - Monocytes: metabolism
KW  - Infant, Newborn
KW  - Cell Differentiation: immunology
KW  - Glycolysis
KW  - Myeloid Cells: metabolism
KW  - Myeloid Cells: immunology
KW  - Adult
KW  - Immunity, Innate
KW  - Female
KW  - Infant
KW  - Male
KW  - Child, Preschool
KW  - Child
KW  - Diet, Ketogenic
KW  - Inflammation: metabolism
KW  - Inflammation: immunology
KW  - Sepsis: immunology
KW  - Sepsis: metabolism
KW  - Adolescent
KW  - Transcriptome
LB  - PUB:(DE-HGF)16
C6  - pmid:40050264
C2  - pmc:PMC11885822
DO  - DOI:10.1038/s41467-025-57357-w
UR  - https://pub.dzne.de/record/277424
ER  -