Antiviral Signaling at the Maternal Fetal Interface

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Differences in the antiviral interferon (IFN) response of various cell types within the maternal fetal interface at the placental level are poorly understood. Research has shown that the chorionic villi at the maternal-fetal interface are not very susceptible to viral infection due to constitutive type III IFN expression, while the fetal membrane is highly susceptible to infection. However, whether this permissiveness is due to lack of IFN signaling capacity in the fetal membrane is unknown, as the fetal membrane's antiviral IFN pathways are not well studied.


This study sought to identify the role of different pattern recognition receptors (PRRs) in placental cells derived from the chorionic villi and trophoblast layers, hypothesizing that antiviral IFN signals differ and are reduced in cells derived from the fetal membrane.


Immortalized trophoblast-derived choriocarcinoma cells (JEG3s and BeWos) and primary amniotic epithelial cells (PAECs) were stimulated with synthetic ligands: poly(I:C), 2'3'cGAMP, 3p-hpRNA, and R848 (TLR3, STING, RIG-I, and TLR7/8 agonists, respectively). RT-qPCR was used to analyze gene expression for a panel of representative interferon stimulated genes and type I/type III IFNs, and quanti-blue assay was used to measure secreted embryonic alkaline phosphatase activity in cell culture supernatant to indicate protein level response.


Type III interferon response in JEG3s and BeWos were present, along with evidence of TLR3 signaling which indicates placental cells capability to respond to RNA viruses. Preliminary data shows PAEC showed negligible changes in IFN gene expression.


These data suggest that, with regard to type of stimulation, the IFN response may be skewed to type I or type III depending on the placental cell.  Further research investigating the role of the IFN response in fetal membrane susceptibility to viral infection should analyze whether specific IFNs confer protective immunity, which could inform potential antiviral treatments to prevent maternal and fetal infection by teratogenic viruses.

UPMC Children's Hospital of Pittsburgh
UPMC Children's Hospital of Pittsburgh

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