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

Nat Commun. 2014 Aug 14;5:4649. doi: 10.1038/ncomms5649.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / physiology
  • Bacterial Infections / immunology*
  • Bacterial Infections / physiopathology
  • Bacterial Infections / prevention & control*
  • Glucose / metabolism
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Humans
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology*
  • Infant, Newborn
  • Leukocyte Immunoglobulin-like Receptor B1
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / physiology*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology
  • T-Lymphocytes / physiology

Substances

  • Antigens, CD
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Immunologic
  • Glucose

Associated data

  • GEO/GSE25504