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000277424 037__ $$aDZNE-2025-00407
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000277424 1001_ $$aEhlers, Greta$$b0
000277424 245__ $$aOxidative phosphorylation is a key feature of neonatal monocyte immunometabolism promoting myeloid differentiation after birth.
000277424 260__ $$a[London]$$bSpringer Nature$$c2025
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000277424 520__ $$aNeonates 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.
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000277424 650_2 $$2MeSH$$aOxidative Phosphorylation
000277424 650_2 $$2MeSH$$aHumans
000277424 650_2 $$2MeSH$$aMonocytes: immunology
000277424 650_2 $$2MeSH$$aMonocytes: metabolism
000277424 650_2 $$2MeSH$$aInfant, Newborn
000277424 650_2 $$2MeSH$$aCell Differentiation: immunology
000277424 650_2 $$2MeSH$$aGlycolysis
000277424 650_2 $$2MeSH$$aMyeloid Cells: metabolism
000277424 650_2 $$2MeSH$$aMyeloid Cells: immunology
000277424 650_2 $$2MeSH$$aAdult
000277424 650_2 $$2MeSH$$aImmunity, Innate
000277424 650_2 $$2MeSH$$aFemale
000277424 650_2 $$2MeSH$$aInfant
000277424 650_2 $$2MeSH$$aMale
000277424 650_2 $$2MeSH$$aChild, Preschool
000277424 650_2 $$2MeSH$$aChild
000277424 650_2 $$2MeSH$$aDiet, Ketogenic
000277424 650_2 $$2MeSH$$aInflammation: metabolism
000277424 650_2 $$2MeSH$$aInflammation: immunology
000277424 650_2 $$2MeSH$$aSepsis: immunology
000277424 650_2 $$2MeSH$$aSepsis: metabolism
000277424 650_2 $$2MeSH$$aAdolescent
000277424 650_2 $$2MeSH$$aTranscriptome
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000277424 7001_ $$00009-0002-7392-6384$$aTödtmann, Annika Marie$$b1
000277424 7001_ $$0P:(DE-2719)9001067$$aHolsten, Lisa$$b2$$eFirst author
000277424 7001_ $$00000-0002-8190-273X$$aWillers, Maike$$b3
000277424 7001_ $$aHeckmann, Julia$$b4
000277424 7001_ $$aSchöning, Jennifer$$b5
000277424 7001_ $$aRichter, Maximilian$$b6
000277424 7001_ $$aHeinemann, Anna Sophie$$b7
000277424 7001_ $$00000-0002-3624-6251$$aPirr, Sabine$$b8
000277424 7001_ $$aHeinz, Alexander$$b9
000277424 7001_ $$aDopfer, Christian$$b10
000277424 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b11
000277424 7001_ $$0P:(DE-2719)2812750$$aBecker, Matthias$$b12
000277424 7001_ $$aBüchel, Johanna$$b13
000277424 7001_ $$aWöckel, Achim$$b14
000277424 7001_ $$00000-0001-5554-1937$$avon Kaisenberg, Constantin$$b15
000277424 7001_ $$aHansen, Gesine$$b16
000277424 7001_ $$00000-0001-9322-5820$$aHiller, Karsten$$b17
000277424 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b18
000277424 7001_ $$aHärtel, Christoph$$b19
000277424 7001_ $$00000-0002-3835-1485$$aKastenmüller, Wolfgang$$b20
000277424 7001_ $$00000-0001-8974-7052$$aVaeth, Martin$$b21
000277424 7001_ $$0P:(DE-2719)9000845$$aUlas, Thomas$$b22$$udzne
000277424 7001_ $$00000-0002-9009-3559$$aViemann, Dorothee$$b23
000277424 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-57357-w$$gVol. 16, no. 1, p. 2239$$n1$$p2239$$tNature Communications$$v16$$x2041-1723$$y2025
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