During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti-parasitic type 2 helper T-cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen-presenting cell-independent manner, by modulating the Th2-specific transcriptional program. Adult schistosomes secrete miRNA-harboring extracellular vesicles that are internalized by Th cells in vitro. Schistosomal miRNAs are found also in T helper cells isolated from Peyer's patches and mesenteric lymph nodes of infected mice. In T helper cells, the schistosomal miR-10 targets MAP3K7 and consequently downmodulates NF-κB activity, a critical transcription factor for Th2 differentiation and function. Our results explain, at least partially, how schistosomes tune down the Th2 response, and provide further insight into the reciprocal geographic distribution between high prevalence of parasitic infections and immune disorders such as allergy. Furthermore, this worm-host crosstalk mechanism can be harnessed to develop diagnostic and therapeutic approaches for human schistosomiasis and Th2-associated diseases.

中文翻译：

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血吸虫细胞外囊泡封闭的 miRNA 调节宿主 T 辅助细胞分化。


在血吸虫感染的慢性阶段，雌性会产下受精卵，引发强烈的抗寄生虫 2 型辅助 T 细胞 (Th2) 免疫反应。目前尚不清楚这种 Th2 反应如何逐渐减弱，尽管线虫可以存活多年并继续产卵。在这里，我们发现曼氏血吸虫通过调节 Th2 特异性转录程序，以不依赖于抗原呈递细胞的方式下调 Th2 分化。成体血吸虫分泌含有 miRNA 的细胞外囊泡，在体外被 Th 细胞内化。从受感染小鼠的派尔氏淋巴结和肠系膜淋巴结中分离出的 T 辅助细胞中也发现了血吸虫 miRNA。在 T 辅助细胞中，血吸虫 miR-10 靶向 MAP3K7，从而下调 NF-κB 活性，NF-κB 是 Th2 分化和功能的关键转录因子。我们的结果至少部分地解释了血吸虫如何调节 Th2 反应，并进一步深入了解寄生虫感染高发率与过敏等免疫疾病之间的相互地理分布。此外，这种蠕虫-宿主串扰机制可用于开发人类血吸虫病和 Th2 相关疾病的诊断和治疗方法。