Prenatal exposure to Zika virus shapes offspring neutrophil function in a sex-specific manner.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-03 DOI:10.1038/s41467-025-63941-x

Jiahui Ding,Anna Hu,Annie Thy Nguyen,Grace M Swanson,Aditi Singh,Nicholas Adzibolosu,Diana Manchorova,Elizabeth Findeis,Anthony Maxwell,Yuan He,Marta Rodriguez Garcia,Gil Mor

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Abstract

Maternal viral infection during pregnancy can have lasting consequences on offspring immune development. Zika virus (ZIKV) is known to trigger maternal immune activation (MIA), yet its impact on fetal and postnatal innate immunity remains poorly understood. Here, we investigate how prenatal exposure to ZIKV influences offspring neutrophil function using a murine model of maternal infection. We identify a sex-dimorphic placental response to ZIKV and observed hyperinflammation in ZIKV-exposed male offspring following LPS challenge. Functional assays reveal impaired reactive oxygen species production and defective neutrophil extracellular trap formation in neutrophils from ZIKV-exposed offspring. Furthermore, we identify A20 as a key sex-dimorphic regulator of neutrophil activation and survival. Here, we show that maternal viral infection during pregnancy programs long-term offspring immunity in a sex-specific manner, providing insights into the developmental origins of differential susceptibility to infections and inflammatory diseases later in life.

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产前接触寨卡病毒会以性别特异性的方式影响后代的中性粒细胞功能。

母亲在怀孕期间感染病毒会对后代的免疫发育产生持久的影响。寨卡病毒（ZIKV）已知可触发母体免疫激活（MIA），但其对胎儿和产后先天免疫的影响仍知之甚少。在这里，我们研究如何产前暴露于寨卡病毒影响后代中性粒细胞功能使用小鼠模型的母体感染。我们发现胎盘对寨卡病毒的性别二态反应，并观察到在LPS刺激下暴露于寨卡病毒的雄性后代出现过度炎症。功能分析显示，暴露于寨卡病毒的后代的中性粒细胞中活性氧产生受损和中性粒细胞胞外陷阱形成缺陷。此外，我们发现A20是中性粒细胞活化和存活的关键性别二态调节因子。在这里，我们表明，母亲在怀孕期间的病毒感染以性别特异性的方式计划了长期的后代免疫，为以后生活中对感染和炎症性疾病的不同易感性的发育起源提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.