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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Identification of a human neonatal immune-metabolic network associated with bacterial infection
Nature Communications, Volume 5, Article 4649, Year 2014
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Description
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. © 2014 Macmillan Publishers Limited. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4143936/bin/ncomms5649-s1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC4143936/bin/ncomms5649-s2.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC4143936/bin/ncomms5649-s3.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC4143936/bin/ncomms5649-s4.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC4143936/bin/ncomms5649-s5.xls
Authors & Co-Authors
Smith, Claire L.
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
United Kingdom, Edinburgh
The University of Edinburgh
Dickinson, Paul
United Kingdom, Edinburgh
The University of Edinburgh
Forster, Thorsten
United Kingdom, Edinburgh
The University of Edinburgh
Craigon, Marie
United Kingdom, Edinburgh
The University of Edinburgh
Ross, Alan
United Kingdom, Edinburgh
The University of Edinburgh
Khondoker, Mizanur R.
United Kingdom, Edinburgh
The University of Edinburgh
United Kingdom, London
King's College London
France, Rebecca
United Kingdom, Edinburgh
The University of Edinburgh
Ivens, Alasdair C.
United Kingdom, Edinburgh
Fios Genomics Ltd.
United Kingdom, Edinburgh
The University of Edinburgh
Lynn, David J.
Ireland, Carlow
Teagasc - Irish Agriculture and Food Development Authority
Australia, Adelaide
South Australian Health and Medical Research Institute
Orme, Judith
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Jackson, Allan
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Lacaze, Paul
United Kingdom, Edinburgh
The University of Edinburgh
Flanagan, Katie L.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Australia, Clayton
Monash University
Stenson, Ben James
United Kingdom, Edinburgh
Mrc Centre for Reproductive Health
Ghazal, Peter
United Kingdom, Edinburgh
The University of Edinburgh
Statistics
Citations: 15
Authors: 15
Affiliations: 8
Identifiers
Doi:
10.1038/ncomms5649
e-ISSN:
20411723
Research Areas
Genetics And Genomics
Health System And Policy
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cross Sectional Study