期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms5649
关键词
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资金
- Wellcome Trust [WT066784]
- EU
- Chief Scientists Office [ETM202]
- BBSRC [BB/D019621/1]
- Centre for Synthetic and Systems Biology at Edinburgh (SynthSys)
- BBSRC
- EPSRC [BB/D019621/1]
- MRC [G0701291]
- Teagasc [RMIS6018]
- Biotechnology and Biological Sciences Research Council [BB/D019621/1] Funding Source: researchfish
- Chief Scientist Office [ETM/202] Funding Source: researchfish
- Medical Research Council [MC_EX_G0701291, G0701289] Funding Source: researchfish
- BBSRC [BB/D019621/1] Funding Source: UKRI
- MRC [G0701289, MC_EX_G0701291] Funding Source: UKRI
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.
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