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

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 postchallenge 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.

Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes

“…While this approach revealed that chorioamnionitis exposure altered gene expression in both innate and adaptive immune pathways, the approach made it impossible to determine which cells were responsible for these differences. A more recent study performed RNA‐seq on purified cord blood monocytes from very preterm neonates (<32 weeks) with and without chorioamnionitis exposure both before and after stimulation with the most common etiology of neonatal late onset sepsis, Staphylococcus epidermidis . This study found that chorioamnionitis exposure in preterm infants is associated with a hyporesponsive transcriptional profile, which may alter a preterm infants’ risk of sepsis.…”

Immunology & Cell Biology Publication of the Year Awards 2018

“…The Original Article by Emma de Jong et al ., “Exposure to chorioamnionitis alters the monocyte transcriptional response to the neonatal pathogen Staphylococcus epidermidis ”, was published in September 2018, is the winner of the Thermo Fisher Scientific Publication Award for 2018 . Dr de Jong and colleagues investigated the impact of chorioamnionitis, an infection of the placenta or amniotic fluid, on monocyte responses using whole transcriptome sequencing.…”

Chorioamnionitis exposure dampens the preterm monocyte response to subsequent challenges

“…The recent paper by de Jong et al . describes the influence of chorioamnionitis exposure on preterm monocyte transcription using whole transcriptome shotgun sequencing (RNA‐seq), which provides valuable information on the impact of this inflammatory exposure on neonatal innate immune function in a cell‐specific manner …”

“…The recent paper by de Jong et al describes the influence of chorioamnionitis exposure on preterm monocyte transcription using whole transcriptome shotgun sequencing (RNA-seq), which provides valuable information on the impact of this inflammatory exposure on neonatal innate immune function in a cellspecific manner. 3 Exposure to chorioamnionitis increases the risk of developing earlyonset sepsis (within the first 72 h of birth) with conflicting data about whether it is protective against or increases susceptibility to late-onset sepsis (after 72 h of life), 1,4,5 suggesting that exposure to chorioamnionitis impacts subsequent neonatal immune function and modulates the already high infection risk in the neonatal period. Previous studies have utilized microarrays on umbilical cord blood of preterm infants exposed to chorioamnionitis and/or FIRS to evaluate the impact of this inflammatory exposure on the neonatal immune transcriptosome.…”

“…The recent paper by de Jong et al addressed these deficiencies by performing RNA-seq on preterm umbilical cord blood purified monocytes with and without chorioamnionitis exposure both before and after stimulation with Staphylococcus epidermidis, the most common cause of neonatal late-onset sepsis. 3 They found that chorioamnionitis exposure was associated with a hypo-responsive transcriptional profile upon stimulation with S. epidermidis, with downregulation of genes involved in antigen presentation and adaptive immune responses. They postulate that this dampened immune response contributes to the heightened sepsis risk experienced by these infants (Figure 1).…”