Abstract
SUMMARY Interferon lambda (IFN-λ, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-λ during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-⍺β receptor ( Ifnar1 -/- ) or both the IFN-⍺β and IFN-λ receptors ( Ifnar1 -/- Ifnlr1 -/- ) at E9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission. We used HiPlex RNAscope on entire gravid uteruses and found that IFN-λ 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-λ responsive cell type mediating protection against ZIKV congenital infection.
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SUMMARY
Interferon lambda (IFN-λ, type III IFN) mediates antiviral immunity at anatomic barriers, including the maternal-fetal interface. To investigate the effects of IFN-λ during congenital Zika virus (ZIKV) infection, we infected mice lacking the IFN-⍺β receptor (Ifnar1-/-) or both the IFN-⍺β and IFN-λ receptors (Ifnar1-/-Ifnlr1-/-) at E9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission. We used HiPlex RNAscope on entire gravid uteruses and found that IFN-λ 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-λ responsive cell type mediating protection against ZIKV congenital infection.
Competing Interest Statement
The authors have declared no competing interest.
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