Identification of a human neonatal immune-metabolic network associated with bacterial infection.
Nat Commun
; 5: 4649, 2014 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-25120092
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
/
Redes e Vias Metabólicas
/
Imunidade Inata
Tipo de estudo:
Diagnostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Newborn
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2014
Tipo de documento:
Article