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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Perinatal inflammation influences but does not arrest rapid immune development in preterm babies
S Kamdar1, R Hutchinson2,3, A Laing1
1Peter Gorer Department of Immunobiology, King's College London, London, SE1 9RT, UK.
Insights
Preterm infants can develop adult-like immune function rapidly, independent of their microbiome. However, infections in preterm babies show distinct immune cell differences that may predict clinical outcomes.
Area of Science:
- Neonatal immunology
- Preterm infant health
- Infectious disease complications
Background:
- Preterm birth (<32 weeks gestation) poses significant risks for infection and related mortality.
- Understanding immune system development and its modulation by perinatal factors in preterm infants is limited.
Purpose of the Study:
- To prospectively and longitudinally investigate immune system development in preterm infants.
- To identify how perinatal factors, including infection, influence immune maturation.
- To explore potential predictors of infection-related outcomes in this population.
Main Methods:
- Longitudinal cohort study of infants born before 32 weeks gestation.
- Assessment of immune cell functionality, including T cell responses (CXCL8, TNF).
- Analysis of immune maturation in relation to microbiome development and infection history.
Main Results:
- Preterm infants demonstrate rapid acquisition of adult-level immune functionality, irrespective of microbiome diversity.
- Infants exposed to in utero or postnatal infection showed reduced CXCL8-producing T cells but comparable TNF-producing T cells.
- These immune differences preceded an unstable postnatal clinical course.
Conclusions:
- Rapid immune maturation is achievable in preterm infants.
- Specific T cell functional differences can be identified following infection exposure.
- These immune markers may serve as predictors for subsequent infection-mediated outcomes in preterm infants.
Abstract:
Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation. We demonstrate that preterm babies, including those born extremely prematurely (<28 weeks), are capable of rapidly acquiring some adult levels of immune functionality, in which immune maturation occurs independently of the developing heterogeneous microbiome. By contrast, we observe a reduced percentage of CXCL8-producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course. These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes.
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