Innate immune cells have been acknowledged as trainable in recent years. While intestinal tuft cells are recognized for their crucial roles in the host defense against intestinal pathogens, there remains uncertainty regarding their trainability. Enterovirus 71 (EV71), a prevalent enterovirus that primarily infects children but rarely infects adults. At present, there is a significant expansion of intestinal tuft cells in the EV71-infected mouse model, which is associated with EV71-induced interleukin-25 (IL-25) production. Further, we found that IL-25 pre-treatment at 2 weeks old mouse enabled tuft cells to acquire immune memory. This was evidenced by the rapid expansion and stronger response of IL-25-trained tuft cells in response to EV71 infection at 6 weeks old, surpassing the reactivity of naïve tuft cells in mice without IL-25-trained progress. Interestingly, IL-25-trained intestinal tuft cells exhibit anti-enteroviral effect via producing a higher level of IL-25. Mechanically, IL-25 treatment upregulates spermidine/spermine acetyl-transferase enzyme (SAT1) expression, mediates intracellular polyamine deficiency, further inhibits enterovirus replication. In summary, tuft cells can be trained by IL-25, which supports faster and higher level IL-25 production in response to EV71 infection and further exhibits anti-enteroviral effect via SAT1-mediated intracellular polyamine deficiency. Given that IL-25 can be induced by multiple gut microbes during human growth and development, including shifts in gut flora abundance, which may partially explain the different susceptibility to enteroviral infections between adults and children.

中文翻译：

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婴儿期肠道簇状细胞的训练免疫力增强了宿主对小鼠肠道病毒感染的防御能力。


近年来，先天免疫细胞已被公认为是可训练的。虽然肠道簇状细胞因其在宿主防御肠道病原体中的关键作用而得到认可，但它们的可训练性仍然存在不确定性。肠道病毒 71 （EV71） 是一种流行的肠道病毒，主要感染儿童，但很少感染成人。目前，在 EV71 感染的小鼠模型中，肠道簇状细胞显著扩增，这与 EV71 诱导的白细胞介素 25 （IL-25） 产生有关。此外，我们发现 2 周龄小鼠的 IL-25 预处理使簇状细胞能够获得免疫记忆。IL-25 训练的簇细胞在 6 周龄时响应 EV71 感染的快速扩增和更强的反应证明了这一点，超过了没有 IL-25 训练进展的小鼠中幼稚簇细胞的反应性。有趣的是，IL-25 训练的肠簇细胞通过产生更高水平的 IL-25 表现出抗肠道病毒作用。在机械上，IL-25 处理上调亚精胺/精胺乙酰转移酶 （SAT1） 表达，介导细胞内多胺缺乏症，进一步抑制肠道病毒复制。总之，簇状细胞可以通过 IL-25 进行训练，IL-25 支持更快和更高水平的 IL-25 产生以响应 EV71 感染，并通过 SAT1 介导的细胞内多胺缺乏症进一步表现出抗肠道病毒作用。鉴于 IL-25 可在人类生长发育过程中由多种肠道微生物诱导，包括肠道菌群丰度的变化，这可能部分解释了成人和儿童对肠道病毒感染的不同易感性。