Interferon lambda signaling to maternal dendritic cells protects against congenital Zika virus infection

Interferon lambda (IFN-{lambda}, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-{lambda} during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-{beta} receptor (Ifnar1-/-) or both the IFN-{beta} and IFN-{lambda} receptors (Ifnar1-/-Ifnlr1-/-) at E9 and found that loss of maternal IFN-{lambda} signaling resulted in greater transplacental transmission. We used HiPlex RNAscope on entire gravid uteruses and found that IFN-{lambda} was expressed more proximal to the site of ZIKV infection in Ifnar1-/- dams compared to Ifnar1-/-Ifnlr1-/- dams. We performed immunophenotyping of the placenta and uterus by flow cytometry and found a decrease in dendritic cells and NK cells in the uterus of Ifnar1-/-Ifnlr1-/- dams compared to Ifnar1-/- dams, but NK cell depletion did not impact fetal infection. Using conditional knockout mice, we identified maternal dendritic cells as the key IFN-{lambda} responsive cell type mediating protection against ZIKV congenital infection.