Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood

Birte Tröger*, Mathias Heidemann, Ines Osthues, Dennis Knaack, Wolfgang Göpel, Egbert Herting, Johannes K.M. Knobloch, Christoph Härtel

*Corresponding author for this work
1 Citation (Scopus)


Background: Coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis are highly prevalent pathogens for sepsis in neonates. The interaction between host, environment and pathogenic factors of S. epidermidis are still poorly understood. Our objective was to address the role of several pathogenic factors of S. epidermidis on neonatal cytokine responses and to characterize the influence of three immunomodulatory drugs. Methods: We performed an ex-vivo model of S. epidermidis sepsis by assessment of blood cytokine production in neonatal whole blood stimulation assays (ELISA). S. epidermidis strains with different characteristics were added as full pathogen to umbilical cord blood cultures and the influence of indomethacin, ibuprofen and furosemide on neonatal immune response to S. epidermidis was evaluated (Flow cytometry). Results: Stimulation with S. epidermidis sepsis strains induced higher IL-6 and IL-10 expression than stimulation with colonization strains. Biofilm formation in clinical isolates was associated with increased IL-10 but not IL-6 levels. In contrast, stimulation with mutant strains for biofilm formation and extracellular virulence factors had no major effect on cytokine expression. Notably, addition of ibuprofen or indomethacin to S. epidermidis inoculated whole blood resulted in mildly increased expression of TNF-α but not IL-6, while frusemide decreased the production of pro-inflammatory cytokines, i.e. IL-6 and IL-8. Conclusions: The virulence of sepsis strains is coherent with increased cytokine production in our whole-blood in-vitro sepsis model. Biofilm formation and expression of extracellular virulence factors had no major influence on readouts in our setting. It is important to acknowledge that several drugs used in neonatal care have immunomodulatory potential.

Original languageEnglish
JournalJournal of Microbiology, Immunology and Infection
Issue number2
Pages (from-to)240-249
Number of pages10
Publication statusPublished - 04.2020

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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