Decidual cells are the initial target of polyriboinosinic–polyribocytidylic acid in a mouse model of maternal viral infection

Abstract

Background: Maternal immune activation has been implicated in the pathophysiology of neurodevelopmental disorders such as autism spectrum disorders caused by maternal infection. It has been suggested that the placental origin of inflammatory cytokines leads to neurodevelopmental disorders. However, the identity of the initial immune-activated site in the placenta, in response to maternal viral infection, is not clear. Methods: By cross-breeding male enhanced green fluorescent protein (EGFP) transgenic mice with wild-type females, the placental tissues of maternal origin can be distinguished from those of paternal origin by EGFP expression. Using this method, at embryonic day (E) 12.5, dams were administered an intraperitoneal polyriboinosinic–polyribocytidylic acid (poly [I:C]) injection. We quantitatively analyzed the levels of phosphorylated interferon (IFN) regulatory factor 3 (pIRF3) in the placenta, and investigated the distribution of pIRF3 positive cells. Results: We show that maternally derived decidual cells are the initial target of maternal poly (I:C) through the toll-like receptor 3/TIR-domain-containing the adapter-inducing interferon-β signaling pathway. We also show that the expression of interferon-β was upregulated in the placenta after maternal injection with poly (I:C). Conclusion: These results suggest that maternally derived decidual cells are the initial target of maternal poly (I:C) and that this innate immune response is likely associated with a state of maternal immune activation.

Keywords

• Maternal immune activation
• Placenta
• Decidual cells
• Polyriboinosinic–polyribocytidylic acid
• Toll-like receptor 3 signaling
• Phosphorylation of interferon regulatory factor 3