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

Dedloff, M. R.; Reinhardt, T. R.; Ropp, T.-J. F.; Rivera-Cardona, J.; Robles, C. R.; Casazza, R. L.; Ezzell, J. A.; Itano, M. S.; Lazear, H. M.

doi:10.64898/2026.01.25.701624

bioRxiv · 10.64898/2026.01.25.701624

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

Dedloff, M. R.·Reinhardt, T. R.·Ropp, T.-J. F.·Rivera-Cardona, J.·Robles, C. R.·Casazza, R. L.·Ezzell, J. A.·Itano, M. S.·Lazear, H. M.

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Abstract

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.

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Dedloff, M. R., Reinhardt, T. R., Ropp, T.-J. F., Rivera-Cardona, J., Robles, C. R., Casazza, R. L., Ezzell, J. A., Itano, M. S., Lazear, H. M.. 2026-01-27. Interferon lambda signaling to maternal dendritic cells protects against congenital Zika virus infection. https://doi.org/10.64898/2026.01.25.701624

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