Impaired cellular energy metabolism in cord blood macrophages contributes to abortive response toward inflammatory threats

Stephan Dreschers, Kim Ohl, Michael Lehrke, Julia Möllmann, Bernd Denecke, Ivan Costa, Thomas Vogl, Dorothee Viemann, Johannes Roth, Thorsten Orlikowsky () and Klaus Tenbrock
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Stephan Dreschers: RWTH Aachen University
Kim Ohl: RWTH Aachen University
Michael Lehrke: RWTH Aachen University
Julia Möllmann: RWTH Aachen University
Bernd Denecke: RWTH Aachen University
Ivan Costa: RWTH Aachen University
Thomas Vogl: University of Münster
Dorothee Viemann: Medical University of Hannover (MHH)
Johannes Roth: University of Münster
Thorsten Orlikowsky: RWTH Aachen University
Klaus Tenbrock: RWTH Aachen University

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Neonatal sepsis is characterized by hyperinflammation causing enhanced morbidity and mortality compared to adults. This suggests differences in the response towards invading threats. Here we investigate activated cord blood macrophages (CBMΦ) in comparison to adult macrophages (PBMΦ), indicating incomplete interferon gamma (IFN-γ) and interleukin 10 (IL-10)-induced activation of CBMΦ. CBMΦ show reduced expression of phagocytosis receptors and cytokine expression in addition to altered energy metabolism. In particular, IFN-γ as well as IL-10-activated CBMΦ completely fail to increase glycolysis and furthermore show reduced activation of the mTOR pathway, which is important for survival in sepsis. MTOR inhibition by rapamycin equalizes cytokine production in CBMΦ and PBMΦ. Finally, incubation of PBMΦ with cord blood serum or S100A8/A9, which is highly expressed in neonates, suppresses mTOR activation, prevents glycolysis and the expression of an PBMΦ phenotype. Thus, a metabolic alteration is apparent in CBMΦ, which might be dependent on S100A8/A9 expression.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09359-8

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DOI: 10.1038/s41467-019-09359-8

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