{"id":385,"title":"Interferon-λ signaling to maternal dendritic cells protects against congenital Zika virus infection","title_zh":"IFN-λ信号作用于母体树突状细胞可防止先天性寨卡病毒感染","url":"https://pubmed.ncbi.nlm.nih.gov/42912987","doi":"10.1126/sciadv.aeh1073","pmid":"42912987","journal":"Sci Adv","kind":"paper","lang":"en","published_at":"2026-10-23T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Dedloff MR","Reinhardt TR","Ropp TF","Rivera-Cardona J","Robles CR","Casazza RL","Ezzell JA","Itano MS","Lazear HM"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":3.0,"hits":["maternal-fetal interface","placenta","uterus"]},{"slug":"animal-models","score":0.8,"hits":["knockout mice"]}],"topic_score":3.0,"preference_score":0.0,"preference_labels":[],"llm_score":73.0,"final_score":81.0,"score_dims":{"novelty":80,"rigor":88,"impact":68,"relevance":56,"translation":40},"recommend_reason":"研究设计扎实（双敲除与条件敲除、全子宫空间转录定位、流式免疫表型），首次把母胎界面III型干扰素的保护作用落实到母体树突状细胞这一具体细胞类型，对理解妊娠期抗病毒免疫与先天性感染机制有参考价值；但属动物感染模型，与ART临床操作距离较远。","keywords":["IFN-λ","寨卡病毒","母胎界面","树突状细胞","先天性感染","胎盘免疫"],"selected":1,"story_id":331,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"sci-adv","journal_tier":"cns-sub","journal_if":11.7,"is_mock":false,"summary_zh":"研究在胚胎第9天感染寨卡病毒的孕鼠模型中，比较缺失IFN-αβ受体（Ifnar1-/-）与同时缺失IFN-αβ和IFN-λ受体（Ifnar1-/-Ifnlr1-/-）的小鼠，发现母体IFN-λ信号缺失后，经胎盘传播增加，提示IFN-λ在母胎界面具有保护作用。作者用全妊娠子宫HiPlex RNAscope定位发现，Ifnar1-/-孕鼠中IFN-λ表达更靠近感染灶；流式免疫表型显示，Ifnlr1缺失时子宫树突状细胞与NK细胞减少，但清除NK细胞不影响胎儿感染。条件性敲除实验进一步确定母体树突状细胞是介导保护的关键IFN-λ应答细胞。结论：IFN-λ作用于母体树突状细胞，促使其在子宫聚集，从而限制寨卡病毒的先天性感染。","summary":"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.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}