Cytokine profiles of umbilical cord blood mononuclear cells upon in vitro stimulation with lipopolysaccharides of different vaginal gram-negative bacteria

PLoS One. 2019 Sep 19;14(9):e0222465. doi: 10.1371/journal.pone.0222465. eCollection 2019.

Abstract

Inflammatory immune responses induced by lipopolysaccharides (LPS) of gram-negative bacteria play an important role in the pathogenesis of preterm labor and delivery, and in neonatal disorders. To better characterize LPS-induced inflammatory response, we determined the cytokine profile of umbilical cord blood mononuclear cells (UBMC) stimulated with LPS of seven vaginal gram-negative bacteria commonly found in pregnant women with preterm labor and preterm rupture of membrane. UBMC from ten newborns of healthy volunteer mothers were stimulated with purified LPS of Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter calcoaceticus, Citrobacter freundii, and Pseudomonas aeruginosa. UBMC supernatants were tested for the presence of secreted pro-inflammatory cytokines (IL-6, IL-1β, TNF), anti-inflammatory cytokine (IL-10), TH1-type cytokines (IL-12, IFN-γ), and chemokines (IL-8, MIP-1α, MIP-1β, MCP-1) by Luminex technology. The ten cytokines were differentially induced by the LPS variants. LPS of E. coli and E. aerogenes showed the strongest stimulatory activity and P. aeruginosa the lowest. Interestingly, the ability of UBMC to respond to LPS varied greatly among donors, suggesting a strong individual heterogeneity in LPS-triggered inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter calcoaceticus / metabolism
  • Adult
  • Citrobacter freundii / metabolism
  • Cytokines / metabolism*
  • Enterobacter aerogenes / metabolism
  • Escherichia coli / metabolism
  • Female
  • Fetal Blood / cytology*
  • Fetal Membranes, Premature Rupture / metabolism
  • Gram-Negative Bacteria / metabolism*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Obstetric Labor, Premature / microbiology
  • Pregnancy
  • Pseudomonas aeruginosa / metabolism
  • Vagina / microbiology*
  • Young Adult

Substances

  • Cytokines
  • Lipopolysaccharides

Supplementary concepts

  • Preterm Premature Rupture of the Membranes

Grants and funding

This work was supported by institutional research funds of the University of Regensburg to BSG. MT receives salary from MicroBIOMIX and LD receives salary from Lophius Biosciences. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.