Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection
Year: 2026
Type: article
Abstract: Interferon-λ (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-αβ receptor ( Ifnar1 −/− ) or both the IFN-αβ and IFN-λ receptors ( Ifnar1 −/− Ifnlr1 −/− ) at embryonic day 9 and found that loss of maternal IFN-λ signaling resulted in greater transplacental transmission, highlighting a protective effect of IFN-λ at the maternal-fetal interface. To investigate the spatial relationship between ZIKV infection and antiviral responses, we used HiPlex RNAscope on the entire gravid uterus 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 natural killer (NK) cells in the uterus of Ifnar1 −/− Ifnlr1 −/− dams compared to Ifnar1 −/− dams, but NK cell depletion did not affect 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. Together, our data support a model in which IFN-λ signaling to maternal dendritic cells increases dendritic cell accumulation in the uterus, which facilitates a protective antiviral response that restricts ZIKV congenital infection.
Source: Science Advances
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: Howard Hughes Medical Institute, Burroughs Wellcome Fund, Bill and Melinda Gates Foundation, John Templeton Foundation, Paul G. Allen Family Foundation, Morris Animal Foundation, Blue Cross and Blue Shield of Florida Foundation, Leakey Foundation, National Geographic Society, University of North Carolina, Natural Science Foundation of Jilin Province, Fondation Brain Canada, Japan Agency for Medical Research and Development, Wellcome Trust, Environmental Restoration and Conservation Agency, Ministerio de Ciencia, Innovación y Universidades, Fulbright Norway, Ministerio de Educación y Ciencias, Michael Smith Health Research BC, British Heart Foundation, European Commission, Commonwealth Scientific and Industrial Research Organisation, Indian Council of Medical Research, Deutsche Forschungsgemeinschaft, Institut National de la Santé et de la Recherche Médicale, Japan Science and Technology Corporation, Ministry of Education, Culture, Sports, Science and Technology, Canada Research Chairs, National Natural Science Foundation of China, Ministry of Education of the People's Republic of China, Austrian Science Fund, Ministry of Science and Technology of the People's Republic of China, Consejo Nacional de Investigaciones Científicas y Técnicas, Fudan University, Shanghai Municipal Education Commission, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Iran National Science Foundation, Stavros Niarchos Foundation, Natural Science Foundation of Jiangxi Province, China Scholarship Council, Ministerio de Ciencia e Innovación, Universitetet i Bergen, Shionogi, Deutsche Krebshilfe, Yildiz Teknik Üniversitesi, Comisión Interministerial de Ciencia y Tecnología, Universität zu Köln, Japan Diabetes Society, Canada First Research Excellence Fund, Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición, Fundación Palarq, National Institutes of Health, University of North Carolina at Chapel Hill, Peder Sather Center for Advanced Study, Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Economic and Social Research Council, National Health and Medical Research Council, Japan Science and Technology Agency, Freiburg Institute for Advanced Studies, Albert-Ludwigs-Universität Freiburg, Instituto de Salud Carlos III, Agencia Estatal de Investigación, Key Technologies Research and Development Program, National Key Research and Development Program of China, Agricultural Science and Technology Innovation Program, National Major Science and Technology Projects of China, National Defense Science and Technology Innovation Fund of the Chinese Academy of Sciences, Henan Provincial Science and Technology Research Project, Science and Technology Innovation Talents in Universities of Henan Province, NIHR Cambridge Biomedical Research Centre, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Biomedical Imaging and Bioengineering, National Institute of Dental and Craniofacial Research, Jonsson Comprehensive Cancer Center, Eunice Kennedy Shriver National Institute of Child Health and Human Development, School of Medicine, University of North Carolina at Chapel Hill, Graduate School, University of North Carolina at Chapel Hill
Awards: UNC Initiative for Maximizing Student Development, The role of Interferon lambda signaling in flavivirus transmission and pathogenesis at the maternal-fetal interface, G2522521682, Clinical Translational Research Center for Neurodevelopmental Disorders, Molecular Biology of Viral Diseases Predoctoral Training Grant, Antiviral and immunomodulatory effects of interferon lambda in the skin, Cancer Center Support Grant
OpenAlex ID: W7223301979