Placental and intra-amniotic inflammation are associated with altered fetal immune responses at birth

Research output: Contribution to journalArticle

Abstract

Introduction
High-grade placental inflammation is associated with preterm birth and poor neonatal outcomes. Recent reports suggest that low-grade placental inflammation is common in uncomplicated pregnancies. The relationship between placental inflammation and innate immune anti-microbial responses is unknown. In this study we sought to identify any association between placental inflammation and fetal immune responses.
Methods
Cord blood samples collected from late preterm and full-term Caesarean section deliveries (n = 44) were exposed to various immune challenges (resiquimod, LPS, PGN, poly (I:C), cGAMP, and 5′ppp-dsRNA) and production of inflammatory mediators (G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α) was measured by multiplex assay. Hospital histology reports were used to assess the extent of inflammation in the placenta.
Results
Almost half (47.7%) of placentae examined here showed histological evidence of inflammation. Resiquimod, LPS, and PGN elicited strong inflammatory responses in neonatal cord blood, while poly (I:C), cGAMP, and 5′ppp-dsRNA elicited weaker responses. Fetuses with evidence of chorioamnionitis and fetal inflammatory reaction in their placentae had significantly increased immune responses to cGAMP and 5′ppp-dsRNA (ligands for STING and RIG-I, respectively) and significantly decreased immune responses to poly (I:C) (a TLR3 agonist). Interestingly, STING, RIG-I, and TLR3 are all involved in viral response pathways, suggesting that fetuses exposed to chorioamnionitis or fetal inflammatory reaction might respond differently to viruses postnatally.
Conclusion
Our data suggest that low-level placental inflammation is associated with altered innate cytokine responses at birth.
Original languageEnglish
Pages (from-to)12-23
JournalPlacenta
Volume85
DOIs
Publication statusPublished - Sep 2019

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Parturition
Inflammation
resiquimod
Placenta
Chorioamnionitis
Fetus
Premature Birth
Granulocyte Colony-Stimulating Factor
Interleukin-8
Fetal Blood
Interleukin-1
Cesarean Section
Interleukin-10
Interleukin-6
Histology
Cytokines
Ligands
Viruses
Pregnancy
polyriboinosinic-polyribocytidylic acid

Cite this

@article{53c74898cdf245cd8aab0f795491dc99,
title = "Placental and intra-amniotic inflammation are associated with altered fetal immune responses at birth",
abstract = "IntroductionHigh-grade placental inflammation is associated with preterm birth and poor neonatal outcomes. Recent reports suggest that low-grade placental inflammation is common in uncomplicated pregnancies. The relationship between placental inflammation and innate immune anti-microbial responses is unknown. In this study we sought to identify any association between placental inflammation and fetal immune responses.MethodsCord blood samples collected from late preterm and full-term Caesarean section deliveries (n = 44) were exposed to various immune challenges (resiquimod, LPS, PGN, poly (I:C), cGAMP, and 5′ppp-dsRNA) and production of inflammatory mediators (G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α) was measured by multiplex assay. Hospital histology reports were used to assess the extent of inflammation in the placenta.ResultsAlmost half (47.7{\%}) of placentae examined here showed histological evidence of inflammation. Resiquimod, LPS, and PGN elicited strong inflammatory responses in neonatal cord blood, while poly (I:C), cGAMP, and 5′ppp-dsRNA elicited weaker responses. Fetuses with evidence of chorioamnionitis and fetal inflammatory reaction in their placentae had significantly increased immune responses to cGAMP and 5′ppp-dsRNA (ligands for STING and RIG-I, respectively) and significantly decreased immune responses to poly (I:C) (a TLR3 agonist). Interestingly, STING, RIG-I, and TLR3 are all involved in viral response pathways, suggesting that fetuses exposed to chorioamnionitis or fetal inflammatory reaction might respond differently to viruses postnatally.ConclusionOur data suggest that low-level placental inflammation is associated with altered innate cytokine responses at birth.",
author = "Lisa Stinson and Matt Payne and Jeffrey Keelan",
year = "2019",
month = "9",
doi = "10.1016/j.placenta.2019.08.079",
language = "English",
volume = "85",
pages = "12--23",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Placental and intra-amniotic inflammation are associated with altered fetal immune responses at birth

AU - Stinson, Lisa

AU - Payne, Matt

AU - Keelan, Jeffrey

PY - 2019/9

Y1 - 2019/9

N2 - IntroductionHigh-grade placental inflammation is associated with preterm birth and poor neonatal outcomes. Recent reports suggest that low-grade placental inflammation is common in uncomplicated pregnancies. The relationship between placental inflammation and innate immune anti-microbial responses is unknown. In this study we sought to identify any association between placental inflammation and fetal immune responses.MethodsCord blood samples collected from late preterm and full-term Caesarean section deliveries (n = 44) were exposed to various immune challenges (resiquimod, LPS, PGN, poly (I:C), cGAMP, and 5′ppp-dsRNA) and production of inflammatory mediators (G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α) was measured by multiplex assay. Hospital histology reports were used to assess the extent of inflammation in the placenta.ResultsAlmost half (47.7%) of placentae examined here showed histological evidence of inflammation. Resiquimod, LPS, and PGN elicited strong inflammatory responses in neonatal cord blood, while poly (I:C), cGAMP, and 5′ppp-dsRNA elicited weaker responses. Fetuses with evidence of chorioamnionitis and fetal inflammatory reaction in their placentae had significantly increased immune responses to cGAMP and 5′ppp-dsRNA (ligands for STING and RIG-I, respectively) and significantly decreased immune responses to poly (I:C) (a TLR3 agonist). Interestingly, STING, RIG-I, and TLR3 are all involved in viral response pathways, suggesting that fetuses exposed to chorioamnionitis or fetal inflammatory reaction might respond differently to viruses postnatally.ConclusionOur data suggest that low-level placental inflammation is associated with altered innate cytokine responses at birth.

AB - IntroductionHigh-grade placental inflammation is associated with preterm birth and poor neonatal outcomes. Recent reports suggest that low-grade placental inflammation is common in uncomplicated pregnancies. The relationship between placental inflammation and innate immune anti-microbial responses is unknown. In this study we sought to identify any association between placental inflammation and fetal immune responses.MethodsCord blood samples collected from late preterm and full-term Caesarean section deliveries (n = 44) were exposed to various immune challenges (resiquimod, LPS, PGN, poly (I:C), cGAMP, and 5′ppp-dsRNA) and production of inflammatory mediators (G-CSF, IFN-γ, IL-1β, IL-6, IL-8, IL-10, and TNF-α) was measured by multiplex assay. Hospital histology reports were used to assess the extent of inflammation in the placenta.ResultsAlmost half (47.7%) of placentae examined here showed histological evidence of inflammation. Resiquimod, LPS, and PGN elicited strong inflammatory responses in neonatal cord blood, while poly (I:C), cGAMP, and 5′ppp-dsRNA elicited weaker responses. Fetuses with evidence of chorioamnionitis and fetal inflammatory reaction in their placentae had significantly increased immune responses to cGAMP and 5′ppp-dsRNA (ligands for STING and RIG-I, respectively) and significantly decreased immune responses to poly (I:C) (a TLR3 agonist). Interestingly, STING, RIG-I, and TLR3 are all involved in viral response pathways, suggesting that fetuses exposed to chorioamnionitis or fetal inflammatory reaction might respond differently to viruses postnatally.ConclusionOur data suggest that low-level placental inflammation is associated with altered innate cytokine responses at birth.

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