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Journal of Molecular Medicine

, Volume 96, Issue 2, pp 147–157 | Cite as

Identification of generic and pathogen-specific cord blood monocyte transcriptomes reveals a largely conserved response in preterm and term newborn infants

  • Emma de JongEmail author
  • David G. Hancock
  • Julie Hibbert
  • Christine Wells
  • Peter Richmond
  • Karen Simmer
  • David Burgner
  • Tobias Strunk
  • Andrew J. Currie
Original Article

Abstract

Escherichia coli and Staphylococcus epidermidis are predominant causes of neonatal sepsis, particularly affecting preterm infants. Susceptibility to infection has been attributed to “immature” innate monocyte defences, but no studies have assessed global transcriptional responses of neonatal monocytes to these pathogens. Here, we aimed to identify and characterise the neonatal monocyte transcriptional responses to E. coli and S. epidermidis and the role of common modifiers such as gestational age (GA) and exposure to chorioamnionitis (a common complication of preterm birth) to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (< 32 weeks GA) and term infants (37–40 weeks GA) following standardised challenge with live S. epidermidis or E. coli. The major transcriptional changes induced by either pathogen were highly conserved between infant groups and stimuli, highlighting a common extant neonatal monocyte response to infection, largely mediated by TLR/NF-κB/TREM-1 signalling. In addition, we observed an activated interferon-centred immune response specific to stimulation with E. coli in both preterm and term infants. These data provide novel insights into the functionality of neonatal monocytes at birth and highlight potential pathways that could be targeted to reduce the harmful effects of bacterial-induced inflammation in sepsis. E. coli and S. epidermidis elicit common transcriptional changes in cord monocytes. The common transcriptional response is mediated by TLR/NF-κB/TREM-1 signalling. IFN genes are differentially regulated by E. coli and S. epidermidis in monocytes. These responses are largely unaffected by GA or exposure to chorioamnionitis.

Key messages

  • E. coli and S. epidermidis elicit common transcriptional changes in cord monocytes.

  • The common transcriptional response is mediated by TLR/NF-κB/TREM-1 signalling.

  • IFN-genes are differentially regulated by E. coli and S. epidermidis in monocytes.

  • These responses are largely unaffected by GA or exposure to chorioamnionitis.

Keywords

E. coli Monocyte Preterm RNA-seq S. epidermidis Sepsis 

Notes

Funding information

This project was kindly supported by funding from the National Health & Medical Research Council of Australia, the Princess Margaret Hospital Foundation, and the BrightSpark Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Supplementary material

109_2017_1609_MOESM1_ESM.pdf (737 kb)
ESM 1 (PDF 737 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Medical & Molecular Sciences, School of Veterinary & Life SciencesMurdoch UniversityMurdochAustralia
  2. 2.School of MedicineFlinders UniversityAdelaideAustralia
  3. 3.Centre for Neonatal Research & Education and Division of PaediatricsUniversity of Western AustraliaPerthAustralia
  4. 4.Centre for Stem Cell Systems, Department of Anatomy and Neuroscience, MDHSUniversity of MelbourneMelbourneAustralia
  5. 5.The Walter and Eliza Hall InstituteMelbourneAustralia
  6. 6.Royal Children’s HospitalMurdoch Children’s Research InstituteMelbourneAustralia
  7. 7.Department of PaediatricsUniversity of MelbourneMelbourneAustralia
  8. 8.Department of PaediatricsMonash UniversityMelbourneAustralia
  9. 9.Neonatal Directorate, King Edward Memorial and Princess Margaret HospitalsSubiacoAustralia

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