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Whole blood transcriptional responses of very preterm infants during late-onset sepsis

ABSTRACT: Whole blood transcriptional responses of very preterm infants during late-onset sepsis

PROVIDER: PRJNA576890 | ENA |

REPOSITORIES: ENA

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Whole blood transcriptional responses of very preterm infants during late-onset sepsis

Project description:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. RNA-Seq was performed on peripheral blood samples (6 – 29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n=5), possible LOS (n=4) or no LOS (n=9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.

2020-06-03 | GSE138712 | GEO

Genome-Wide Expression Profiles in Very Low Birth Weight Infants With Neonatal Sepsis

Project description:Bacterial sepsis is associated with high morbidity and mortality in preterm infants. However, diagnosis of sepsis and identification of the causative agent remains challenging. Our aim was to determine genome-wide expression profiles of very low birth weight (VLBW) infants with and without bacterial sepsis and assess differences.

2016-05-29 | E-MTAB-4785 | biostudies-arrayexpress

Identifying immune signatures of sepsis in very preterm babies

Project description:Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combined multi-parameter flow cytometry, single-cell RNA sequencing (scRNAseq) and targeted plasma analysis to prospectively and longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identified a dynamically changing peripheral blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and monocyte HLA-DR expression, which characterized sepsis even when the common clinical marker of inflammation, C-reactive protein (CRP) was not elevated. Furthermore, scRNAseq showed upregulation of amphiregulin in different leukocyte populations during sepsis, which we validated as a plasma analyte that correlated with clinical signs of disease, even when CRP was normal. This study provides new insights into immune pathways associated with early-life sepsis and identifies potential immune analytes as diagnostic adjuncts for sepsis to guide targeted antibiotic prescribing.

2023-11-23 | GSE236099 | GEO

Meconium microbiome of very preterm infants across Germany

Project description:Meconium microbiome of very preterm infants across Germany

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Fetal-derived activated CD83+ γδ T cells expand in preterm infants with sepsis.

Project description:Here, we investigated γδ T cells in a longitudinal cohort of preterm neonates during the first year of life. Our data reveal dynamic postnatal maturation patterns of γδ T cell subsets, which are largely age-dependent. We report on the expansion of fetal-derived γδ T cells in preterm neonates with sepsis. Single cell transcriptome analyses identified HLA-DRhigh and CD83+ γδ T cells in neonatal sepsis.

2024-05-08 | GSE245131 | GEO

Whole blood transcriptional responses of very preterm infants during late-onset sepsis.

Project description: Not available

| S-EPMC7263612 | biostudies-literature

gut microbiota in very low birth weight preterm infants

Project description:Impact of early empiric antibiotic use on the gut microbiota in very low birth weight preterm infants

| PRJEB39734 | ENA

Airway Exosomal miRNA predicts Bronchopulmonary Dysplasis in Extremely Preterm Infants

Project description:We conducted a prospective cohort study with independent Discovery and Validation cohorts, to formulate predictive biomarkers for Bronchopulmonary Dysplasia in extremely preterm infants. Tracheal aspirate samples were collected at birth from extremely preterm infants. Exosomes were extracted from tracheal aspirates and total RNA was extracted from these exosomes from individual samples. miRNA profiling for all ~ 800 miRNAs was conducted on each sample by nanostring platform. This study found that a distinct airway exosomal miRNA sigrature at birth (decreased miR 876-3p) predicts future development of severe Bronchopulmonary Dysplasia in extremely preterm infants.

2017-12-29 | GSE108604 | GEO

Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study.

Project description: Not available

| S-EPMC7903216 | biostudies-literature

Macrophage response in preterm infants compared to term infants

Project description:Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O2) and infections. The underlying mechanisms are still poorly understood. The hypothesis of this study is that dysregulated macrophage activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Cord blood samples of preterm infants (n=14) and term infants (n=19) as well as peripheral blood from healthy adults (n=17) were collected. Age-dependent differences in immune responses of monocyte-derived MÃÂ¤ from preterm infants were characterized and compared to term infants and adults after lipopolysaccharide (LPS) exposure.

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