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A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro
Edith Reuschel1, Martina Toelge2, Sebastian Haeusler1
1University Department of Obstetrics and Gynecology At The Hospital St. Hedwig of The Order of St. John, University of Regensburg, 93049 Regensburg, Germany.
Insights
Bacterial infections during pregnancy trigger immune responses in newborns. Interleukin-8 (IL-8) shows potential for early infection detection in preterm infants, while MIP-1β may influence sex-specific immunity.
Area of Science:
- Perinatal immunology
- Infectious disease pathogenesis
- Neonatal immune response
Background:
- Gram-positive bacterial infections (Enterococcus faecalis, Streptococcus agalacticae, Staphylococcus aureus) during pregnancy are linked to preterm birth and neonatal sepsis.
- The immature perinatal immune system's cytokine response to these infections is crucial in disease development.
- Knowledge gaps exist regarding specific cytokine profiles in response to perinatal bacterial infections.
Purpose of the Study:
- To investigate cytokine and chemokine responses of umbilical blood mononuclear cells (UBMC) to common bacterial pathogens found in preterm labor.
- To identify key immune mediators involved in the pathogenesis of preterm birth and neonatal sepsis.
- To evaluate the diagnostic potential of specific cytokines, like IL-8, for early infection detection.
Main Methods:
- Umbilical blood mononuclear cells (UBMC) were isolated from newborns of mothers in preterm labor.
- UBMC were stimulated with lysates of E. faecalis, S. agalacticae, and S. aureus.
- Eleven inflammatory, anti-inflammatory, TH1/TH2 cytokines, and chemokines were quantified in UBMC culture media.
- IL-8 levels in cord blood of infected preterm neonates were compared to controls.
Main Results:
- Bacterial lysates, particularly S. aureus and S. agalacticae, induced significant cytokine and chemokine production in UBMC.
- Chemokines showed the most robust induction, with MIP-1β levels higher in female than male neonates.
- IL-8 was significantly upregulated in cord blood of preterm neonates with infections compared to controls.
Conclusions:
- Cytokine responses by the immature perinatal immune system play a central role in preterm birth and neonatal sepsis.
- IL-8 demonstrates potential as a biomarker for timely detection of infections in preterm neonates.
- MIP-1β may be an early indicator of sex-specific immune differences, potentially contributing to male vulnerability in preterm birth.
Abstract:
During pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH1/TH2 cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male's vulnerability to preterm birth.

