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Updated: May 24, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ
Pierre Tissières1, Agnieszka Ochoda, Irène Dunn-Siegrist
1Division of Intensive Care, University Hospitals of Geneva, Geneva, Switzerland. pierre.tissieres@bct.aphp.fr
Insights
Extremely premature infants have significantly impaired innate immune responses to bacteria, increasing sepsis risk. Interferon-gamma ex vivo treatment can correct these defects, offering a potential sepsis prevention strategy.
Area of Science:
- Neonatal immunology
- Infectious disease research
- Immune system development
Background:
- Bacterial sepsis poses a significant threat to premature neonates, contributing to high morbidity and mortality.
- The innate immune response to bacterial infections in extremely premature infants remains poorly understood.
- Understanding these immune deficiencies is crucial for developing targeted interventions.
Purpose of the Study:
- To compare innate immune functions in extremely premature infants, moderately premature infants, term newborns, and healthy adults.
- To investigate the expression of key innate immune receptors (CD14, TLR2, TLR4, MD-2) in leukocytes.
- To assess cytokine responses and opsonophagocytic activity against common sepsis-causing bacteria.
Main Methods:
- Collected cord blood leukocytes from infants across different gestational ages and from adult controls.
- Quantified surface expression of innate immune receptors using flow cytometry.
- Measured cytokine production and plasma-dependent opsonophagocytosis in response to bacterial stimuli.
- Evaluated the effect of ex vivo interferon-gamma (IFN-γ) treatment on immune cell function.
Main Results:
- Leukocytes from extremely premature infants showed significantly lower expression of bacterial recognition receptors.
- Innate immune responses, including cytokine production and opsonophagocytosis, were severely impaired in premature infants.
- Ex vivo incubation of premature infant leukocytes with IFN-γ for 12 hours restored normal immune responses to bacteria.
Conclusions:
- Premature infants exhibit profound defects in innate immunity, explaining their susceptibility to bacterial sepsis.
- The fetal innate immune system undergoes maturation in the final trimester of gestation.
- Ex vivo IFN-γ treatment demonstrates a promising proof-of-concept for preventing neonatal sepsis by enhancing innate immune responses.
Background:
Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.
Methodology/Principal Findings:
We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.
Conclusion/Significance:
Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.
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