Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis

de Jong, E; Hancock, DG; Wells, C; Richmond, P; Simmer, K; Burgner, D; Strunk, T; Currie, AJ

Author(s): de Jong, E; Hancock, DG; Wells, C; Richmond, P; Simmer, K; Burgner, D; Strunk, T; Currie, AJ;
Details: Publication Year 2018-03-13,Volume 96,Issue #8,Page 792-804
Journal Title: Immunology and Cell Biology
Publication Type: Journal Article
Abstract: Preterm infants are uniquely susceptible to late-onset sepsis that is frequently caused by the skin commensal Staphylococcus epidermidis. Innate immune responses, particularly from monocytes, are a key protective mechanism. Impaired cytokine production by preterm infant monocytes is well described, but few studies have comprehensively assessed the corresponding monocyte transcriptional response. Innate immune responses in preterm infants may be modulated by inflammation such as prenatal exposure to histologic chorioamnionitis which complicates 40-70% of preterm pregnancies. Chorioamnionitis alters the risk of late-onset sepsis, but its effect on monocyte function is largely unknown. Here we aimed to determine the impact of exposure to chorioamnionitis on the proportions and phenotype of cord blood monocytes using flow cytometry, as well as their transcriptional response to live S. epidermidis. RNA-seq was performed on purified cord blood monocytes from very preterm infants (<32 weeks gestation, with and without chorioamnionitis-exposure) and term infants (37-40 weeks), pre- and post-challenge with live S. epidermidis. Preterm monocytes from infants without chorioamnionitis exposure did not exhibit an intrinsically deficient transcriptional response to S. epidermidis compared to term infants. In contrast, chorioamnionitis exposure was associated with hypo-responsive transcriptional phenotype regarding a subset of genes involved in antigen presentation and adaptive immunity. Overall, our findings suggest that prenatal exposure to inflammation may alter the risk of sepsis in preterm infants partly by modulation of monocyte responses to pathogens. This article is protected by copyright. All rights reserved.
Publisher: Wiley
Research Division(s): Molecular Medicine
PubMed ID: 29533486
Publisher's Version: https://doi.org/10.1111/imcb.12037
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2018-03-19 10:02:31

Last Modified: 2018-10-22 11:25:30