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@ARTICLE{Ehlers:277424,
author = {Ehlers, Greta and Tödtmann, Annika Marie and Holsten, Lisa
and Willers, Maike and Heckmann, Julia and Schöning,
Jennifer and Richter, Maximilian and Heinemann, Anna Sophie
and Pirr, Sabine and Heinz, Alexander and Dopfer, Christian
and Händler, Kristian and Becker, Matthias and Büchel,
Johanna and Wöckel, Achim and von Kaisenberg, Constantin
and Hansen, Gesine and Hiller, Karsten and Schultze, Joachim
L and Härtel, Christoph and Kastenmüller, Wolfgang and
Vaeth, Martin and Ulas, Thomas and Viemann, Dorothee},
title = {{O}xidative phosphorylation is a key feature of neonatal
monocyte immunometabolism promoting myeloid differentiation
after birth.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DZNE-2025-00407},
pages = {2239},
year = {2025},
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.},
keywords = {Oxidative Phosphorylation / Humans / Monocytes: immunology
/ Monocytes: metabolism / Infant, Newborn / Cell
Differentiation: immunology / Glycolysis / Myeloid Cells:
metabolism / Myeloid Cells: immunology / Adult / Immunity,
Innate / Female / Infant / Male / Child, Preschool / Child /
Diet, Ketogenic / Inflammation: metabolism / Inflammation:
immunology / Sepsis: immunology / Sepsis: metabolism /
Adolescent / Transcriptome},
cin = {AG Schultze / AG Becker / PRECISE},
ddc = {500},
cid = {I:(DE-2719)1013038 / I:(DE-2719)5000079 /
I:(DE-2719)1013031},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354) / 352
- Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-354 / G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40050264},
pmc = {pmc:PMC11885822},
doi = {10.1038/s41467-025-57357-w},
url = {https://pub.dzne.de/record/277424},
}