Cellular metabolism constrains innate immune responses in early human ontogeny

Bernard Kan, Christina Michalski, Helen Fu, Hilda H.T. Au, Kelsey Lee, Elizabeth A. Marchant, Maye F. Cheng, Emily Anderson-Baucum, Michal Aharoni-Simon, Peter Tilley, Raghavendra G. Mirmira, Colin J. Ross, Dan S. Luciani, Eric Jan, Pascal M. Lavoie

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Pathogen immune responses are profoundly attenuated in fetuses and premature infants, yet the mechanisms underlying this developmental immaturity remain unclear. Here we show transcriptomic, metabolic and polysome profiling and find that monocytes isolated from infants born early in gestation display perturbations in PPAR-γ-regulated metabolic pathways, limited glycolytic capacity and reduced ribosomal activity. These metabolic changes are linked to a lack of translation of most cytokines and of MALT1 signalosome genes essential to respond to the neonatal pathogen Candida. In contrast, they have little impact on house-keeping phagocytosis functions. Transcriptome analyses further indicate a role for mTOR and its putative negative regulator DNA Damage Inducible Transcript 4-Like in regulating these metabolic constraints. Our results provide a molecular basis for the broad susceptibility to multiple pathogens in these infants, and suggest that the fetal immune system is metabolically programmed to avoid energetically costly, dispensable and potentially harmful immune responses during ontogeny.

Original languageEnglish (US)
Article number4822
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Cellular metabolism constrains innate immune responses in early human ontogeny'. Together they form a unique fingerprint.

  • Cite this

    Kan, B., Michalski, C., Fu, H., Au, H. H. T., Lee, K., Marchant, E. A., Cheng, M. F., Anderson-Baucum, E., Aharoni-Simon, M., Tilley, P., Mirmira, R. G., Ross, C. J., Luciani, D. S., Jan, E., & Lavoie, P. M. (2018). Cellular metabolism constrains innate immune responses in early human ontogeny. Nature communications, 9(1), [4822]. https://doi.org/10.1038/s41467-018-07215-9