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Updated: Jun 13, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions
Khaleda Rahman Qazi1, Dhanapal Govindaraj2, Magalí Martí2
1Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Insights
Extremely preterm infants show altered immune cell (monocyte) characteristics and responses that persist, increasing vulnerability to infections. Probiotic supplementation had limited impact on these immune features.
Area of Science:
- Immunology
- Neonatology
- Microbiology
Background:
- The innate immune system plays a critical role in early life, especially for preterm infants.
- Preterm birth can lead to long-term immune system alterations.
Purpose of the Study:
- To longitudinally analyze peripheral monocyte compartment changes in extremely preterm infants.
- To investigate the impact of probiotic supplementation on monocyte characteristics and immune responses.
Main Methods:
- Longitudinal analysis of peripheral monocytes in extremely preterm infants via flow cytometry.
- Analysis of lipopolysaccharide (LPS)-stimulated cytokine responses, plasma cytokines, and gut microbiota composition.
- Evaluation of probiotic supplementation effects in a randomized, placebo-controlled study.
Main Results:
- Extremely preterm infants exhibited persistent monocyte alterations, exacerbated by chorioamnionitis, with reduced TLR4 expression and impaired LPS-stimulated cytokine responses early post-birth.
- Sepsis was associated with altered pro-inflammatory and IL-10 responses, persisting even at postmenstrual week 36.
- Gut microbiota correlated with monocyte phenotype, while probiotics showed distinct associations with monocyte characteristics but not responsiveness.
Conclusions:
- Monocyte characteristics and function in extremely preterm infants differ significantly from full-term infants.
- These immune deviations persist until the corrected full-term age, potentially increasing susceptibility to microbial challenges.
- Understanding these alterations is crucial for managing preterm infant health and infection risk.
Introduction:
The innate branch of the immune system is important in early life, in particular for infants born preterm.
Methods:
We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively.
Results:
The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness.
Conclusion:
Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.
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