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

Autor: Smith CL; 1] Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK [2] Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK [3]., Dickinson P; 1] Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK [2] SynthSys-Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3JD, UK [3]., Forster T; 1] Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK [2] SynthSys-Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3JD, UK., Craigon M; Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK., Ross A; Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK., Khondoker MR; 1] Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK [2]., France R; Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK., Ivens A; 1] Fios Genomics Ltd., ETTC, King's Buildings, Edinburgh EH9 3JL, UK [2]., Lynn DJ; 1] Animal Bioscience Research Department, AGRIC, Teagasc, Grange, Dunsany, Co. Meath, Ireland [2]., Orme J; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK., Jackson A; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK., Lacaze P; Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK., Flanagan KL; 1] MRC Research Laboratories, Atlantic Boulevard, PO Box 273, Fajara, Gambia [2]., Stenson BJ; Neonatal Unit, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, UK., Ghazal P; 1] Division of Pathway Medicine, Edinburgh Infectious Diseases, University of Edinburgh, Edinburgh EH16 4SB, UK [2] SynthSys-Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3JD, UK.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2014 Aug 14; Vol. 5, pp. 4649. Date of Electronic Publication: 2014 Aug 14.
DOI: 10.1038/ncomms5649
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: