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

Nat Commun. 2019 Apr 11;10(1):1685. doi: 10.1038/s41467-019-09359-8.


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.

MeSH terms

  • Adult
  • Age Factors
  • Calgranulin A / immunology
  • Calgranulin A / metabolism
  • Calgranulin B / immunology
  • Calgranulin B / metabolism
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytotoxicity, Immunologic*
  • Energy Metabolism / immunology*
  • Fetal Blood / cytology
  • Glycolysis / immunology
  • Healthy Volunteers
  • Humans
  • Infant, Newborn
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Primary Cell Culture
  • Sepsis / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / immunology
  • TOR Serine-Threonine Kinases / metabolism


  • Calgranulin A
  • Calgranulin B
  • IL10 protein, human
  • S100A8 protein, human
  • S100A9 protein, human
  • Interleukin-10
  • Interferon-gamma
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus