加州大学David Julius组近日取得一项新成果。经过不懈努力，他们的研究开发出了寄生虫触发上皮细胞串扰来驱动肠-脑信号。这一研究成果于2026年3月25日发表在国际顶尖学术期刊《自然》上。

在这里，研究组表明这些细胞之间的旁分泌信号构成了神经免疫相互作用和肠-脑通信的机制。研究团队发现簇状细胞有两种不同的乙酰胆碱释放机制，尽管缺乏突触囊泡和可兴奋膜。其中包括对寄生虫衍生代谢物的急性释放，随后是2型炎症时发生的构成性“渗漏样”释放。虽然这两种机制都可以激活隐窝EC细胞上的毒蕈碱受体，但只有乙酰胆碱释放的维持模式才能引起足够的血清素水平，以刺激迷走神经传入神经元，从而抑制食物摄入。这种两阶段分泌旁信号机制解释了寄生虫感染如何从最初的无症状阶段发展到有症状的疾病，其中肠-脑轴内的2型免疫和感觉信号通路协同引起保护行为。

据悉，寄生虫感染调节免疫和感觉反应，但这些系统如何协同引起保护行为仍不完全清楚。肠道上皮含有专门的感觉细胞，可以检测病原体和刺激物。这些细胞包括胆碱能簇细胞，它能感知寄生虫并启动2型免疫反应，以及血清素能肠色素（EC）细胞，它能检测刺激物并与传入神经纤维交流，传递伤害性信号。

附：英文原文

Title: Parasites trigger epithelial cell crosstalk to drive gut–brain signalling

Author: Touhara, Kouki K., Xu, Jinhao, Castro, Joel, Liang, Hong-Erh, Li, Guochuan, Brizuela, Mariana, Harrington, Andrea M., Garcia-Caraballo, Sonia, ODonnell, Tracey, Neumann, Daniel, Rossen, Nathan D., Deng, Fei, Schober, Gudrun, Li, Yulong, Locksley, Richard M., Brierley, Stuart M., Julius, David

Issue&Volume: 2026-03-25

Abstract: Parasitic infections modulate both immune and sensory responses, but how these systems collaborate to elicit protective behaviours remains incompletely understood. The gut epithelium contains specialized sensory cells that detect pathogens and irritants. These include cholinergic tuft cells, which sense parasites and initiate type 2 immune responses1,2,3, as well as serotonergic enterochromaffin (EC) cells, which detect irritants and communicate with afferent nerve fibres to transmit nociceptive signals4,5,6. Here we show that paracrine signalling between these cells constitutes a mechanism for neuro–immune interaction and gut–brain communication. We find that tuft cells use two distinct mechanisms of acetylcholine (ACh) release despite lacking synaptic vesicles and excitable membranes. These include acute release in response to parasite-derived metabolites, followed by constitutive ‘leak-like’ release, which occurs with type 2 inflammation. Although both mechanisms can activate muscarinic receptors on crypt-residing EC cells, only the sustained mode of ACh release elicits levels of serotonin sufficient to stimulate vagal afferent neurons that suppress food intake. This two-phase paracrine signalling mechanism explains how parasitic infection progresses from an initial asymptomatic phase to symptomatic established disease, in which type 2 immune and sensory signalling pathways within the gut–brain axis collaborate to evoke protective behaviours.

DOI: 10.1038/s41586-026-10281-5

Source: https://www.nature.com/articles/s41586-026-10281-5