Journal Article

DZNE-2025-00407

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Oxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.

Ehlers, G. ; Tödtmann, A. M. ; Holsten, L. (First author)DZNE* ; Willers, M. ; Heckmann, J. ; Schöning, J. ; Richter, M. ; Heinemann, A. S. ; Pirr, S. ; Heinz, A. ; Dopfer, C. ; Händler, K.DZNE* ; Becker, M.DZNE* ; Büchel, J. ; Wöckel, A. ; von Kaisenberg, C. ; Hansen, G. ; Hiller, K. ; Schultze, J. L.DZNE* ; Härtel, C. ; Kastenmüller, W. ; Vaeth, M. ; Ulas, T.DZNE* ; Viemann, D.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-57357-w

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.

Keyword(s): Oxidative Phosphorylation (MeSH) ; Humans (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: metabolism (MeSH) ; Infant, Newborn (MeSH) ; Cell Differentiation: immunology (MeSH) ; Glycolysis (MeSH) ; Myeloid Cells: metabolism (MeSH) ; Myeloid Cells: immunology (MeSH) ; Adult (MeSH) ; Immunity, Innate (MeSH) ; Female (MeSH) ; Infant (MeSH) ; Male (MeSH) ; Child, Preschool (MeSH) ; Child (MeSH) ; Diet, Ketogenic (MeSH) ; Inflammation: metabolism (MeSH) ; Inflammation: immunology (MeSH) ; Sepsis: immunology (MeSH) ; Sepsis: metabolism (MeSH) ; Adolescent (MeSH) ; Transcriptome (MeSH)

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
2. Modular High Performance Computing and Artificial Intelligence (AG Becker)
3. Platform for Single Cell Genomics and Epigenomics (PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2025

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