Identification of a human neonatal immune-metabolic network associated with bacterial infection

Claire L. Smith, Paul Dickinson, Thorsten Forster, Marie Craigon, Alan Ross, Mizanur R. Khondoker, Rebecca France, Alasdair Ivens, David J. Lynn, Judith Orme, Allan Jackson, Paul Lacaze, Katie L. Flanagan, Benjamin J. Stenson, Peter Ghazal

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53 Citations (Scopus)

Abstract

Understanding how human neonates respond to infection remains incomplete. Here, a system-level investigation of neonatal systemic responses to infection shows a surprisingly strong but unbalanced homeostatic immune response; developing an elevated set-point of myeloid regulatory signalling and sugar-lipid metabolism with concomitant inhibition of lymphoid responses. Innate immune-negative feedback opposes innate immune activation while suppression of T-cell co-stimulation is coincident with selective upregulation of CD85 co-inhibitory pathways. By deriving modules of co-expressed RNAs, we identify a limited set of networks associated with bacterial infection that exhibit high levels of inter-patient variability. Whereas, by integrating immune and metabolic pathways, we infer a patient-invariant 52-gene-classifier that predicts bacterial infection with high accuracy using a new independent patient population. This is further shown to have predictive value in identifying infection in suspected cases with blood culture-negative tests. Our results lay the foundation for future translation of host pathways in advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis.

Original languageEnglish
Article number5649
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 14 Aug 2014

ASJC Scopus subject areas

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

Cite this

Smith, C. L., Dickinson, P., Forster, T., Craigon, M., Ross, A., Khondoker, M. R., ... Ghazal, P. (2014). Identification of a human neonatal immune-metabolic network associated with bacterial infection. Nature Communications, 5, [5649]. https://doi.org/10.1038/ncomms5649