Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood
Standard
Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood. / Tröger, Birte; Heidemann, Mathias; Osthues, Ines; Knaack, Dennis; Göpel, Wolfgang; Herting, Egbert; Knobloch, Johannes K-M; Härtel, Christoph.
In: J MICROBIOL IMMUNOL, Vol. 53, No. 2, 04.2020, p. 240-249.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood
AU - Tröger, Birte
AU - Heidemann, Mathias
AU - Osthues, Ines
AU - Knaack, Dennis
AU - Göpel, Wolfgang
AU - Herting, Egbert
AU - Knobloch, Johannes K-M
AU - Härtel, Christoph
N1 - Copyright © 2018. Published by Elsevier B.V.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.jmii.2018.04.008
DO - 10.1016/j.jmii.2018.04.008
M3 - SCORING: Journal article
C2 - 30146415
VL - 53
SP - 240
EP - 249
JO - J MICROBIOL IMMUNOL
JF - J MICROBIOL IMMUNOL
SN - 1684-1182
IS - 2
ER -