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

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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 journalSCORING: Journal articleResearchpeer-review

Harvard

Tröger, B, Heidemann, M, Osthues, I, Knaack, D, Göpel, W, Herting, E, Knobloch, JK-M & Härtel, C 2020, 'Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood', J MICROBIOL IMMUNOL, vol. 53, no. 2, pp. 240-249. https://doi.org/10.1016/j.jmii.2018.04.008

APA

Tröger, B., Heidemann, M., Osthues, I., Knaack, D., Göpel, W., Herting, E., Knobloch, J. K-M., & Härtel, C. (2020). Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood. J MICROBIOL IMMUNOL, 53(2), 240-249. https://doi.org/10.1016/j.jmii.2018.04.008

Vancouver

Tröger B, Heidemann M, Osthues I, Knaack D, Göpel W, Herting E et al. Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood. J MICROBIOL IMMUNOL. 2020 Apr;53(2):240-249. https://doi.org/10.1016/j.jmii.2018.04.008

Bibtex

@article{b0c012123cf84fcfb13f636a7a2b6f55,
title = "Modulation of S. epidermidis-induced innate immune responses in neonatal whole blood",
abstract = "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.",
keywords = "Journal Article",
author = "Birte Tr{\"o}ger and Mathias Heidemann and Ines Osthues and Dennis Knaack and Wolfgang G{\"o}pel and Egbert Herting and Knobloch, {Johannes K-M} and Christoph H{\"a}rtel",
note = "Copyright {\textcopyright} 2018. Published by Elsevier B.V.",
year = "2020",
month = apr,
doi = "10.1016/j.jmii.2018.04.008",
language = "English",
volume = "53",
pages = "240--249",
journal = "J MICROBIOL IMMUNOL",
issn = "1684-1182",
publisher = "Elsevier Taiwan LLC",
number = "2",

}

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 -