Journal article
Identification of generic and pathogen-specific cord blood monocyte transcriptomes reveals a largely conserved response in preterm and term newborn infants
Journal of Molecular Medicine, Vol.96(2), pp.147-157
2018
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.
Details
- Title
- Identification of generic and pathogen-specific cord blood monocyte transcriptomes reveals a largely conserved response in preterm and term newborn infants
- Authors/Creators
- E. de Jong (Author/Creator) - Murdoch UniversityD.G. Hancock (Author/Creator) - Flinders UniversityJ. Hibbert (Author/Creator) - The University of Western AustraliaC. Wells (Author/Creator) - The University of MelbourneP. Richmond (Author/Creator) - The University of Western AustraliaK. Simmer (Author/Creator) - The University of Western AustraliaD. Burgner (Author/Creator) - The University of MelbourneT. Strunk (Author/Creator) - The University of Western AustraliaA.J. Currie (Author/Creator) - The University of Western Australia
- Publication Details
- Journal of Molecular Medicine, Vol.96(2), pp.147-157
- Publisher
- Springer Verlag
- Identifiers
- 991005540029307891
- Copyright
- © 2017 Springer-Verlag GmbH Germany, part of Springer Nature
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.23 Antibiotics & Antimicrobials
- 1.23.1757 Group B Streptococcus
- Web Of Science research areas
- Genetics & Heredity
- Medicine, Research & Experimental
- ESI research areas
- Clinical Medicine