美国哈佛医学院Stephen D. Liberles研究组发现，一条气道至大脑的感觉通路介导流感引起的疾病。2023年3月8日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，病原体感染会导致一种刻板的疾病状态，涉及神经元协调的行为和生理变化。感染后，免疫细胞释放出细胞因子和其他介质的“风暴”，其中许多是由神经元检测到的；然而，在自然感染过程中唤起疾病行为的反应神经回路和神经-免疫互动机制仍不清楚。阿司匹林和布洛芬等非处方药被广泛用于缓解疾病，其作用是阻断前列腺素E2（PGE2）的合成。一个主要的模型是，PGE2穿过血脑屏障，直接与下丘脑神经元发生作用。

研究人员利用广泛覆盖周边感觉神经元图谱的遗传工具，反而确定了一小部分检测PGE2的舌咽感觉神经元（petrosal GABRA1神经元），它们对小鼠流感诱发的疾病行为至关重要。去除舌咽GABRA1神经元或有针对性地敲除这些神经元中的PGE2受体3（EP3）可消除流感诱导的早期感染期间食物摄入量、水摄入量和移动性的减少，并提高存活率。遗传学指导的解剖图显示，petrosal GABRA1神经元投射到感染后环氧化酶-2表达增加的鼻咽部粘膜区域，并且在脑干中也显示出一种特定的轴突靶向模式。这些发现共同揭示了一个主要的气道到大脑的感觉通路，它检测局部产生的前列腺素，并介导对呼吸道病毒感染的全身性疾病反应。

附：英文原文

Title: An airway-to-brain sensory pathway mediates influenza-induced sickness

Author: Bin, Na-Ryum, Prescott, Sara L., Horio, Nao, Wang, Yandan, Chiu, Isaac M., Liberles, Stephen D.

Issue&Volume: 2023-03-08

Abstract: Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes1,2. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons3,4; yet, the responding neural circuits and neuro–immune interaction mechanisms that evoke sickness behaviour during naturalistic infections remain unclear. Over-the-counter medications such as aspirin and ibuprofen are widely used to alleviate sickness and act by blocking prostaglandin E2 (PGE2) synthesis5. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons2. Here, using genetic tools that broadly cover a peripheral sensory neuron atlas, we instead identified a small population of PGE2-detecting glossopharyngeal sensory neurons (petrosal GABRA1 neurons) that are essential for influenza-induced sickness behaviour in mice. Ablating petrosal GABRA1 neurons or targeted knockout of PGE2 receptor 3 (EP3) in these neurons eliminates influenza-induced decreases in food intake, water intake and mobility during early-stage infection and improves survival. Genetically guided anatomical mapping revealed that petrosal GABRA1 neurons project to mucosal regions of the nasopharynx with increased expression of cyclooxygenase-2 after infection, and also display a specific axonal targeting pattern in the brainstem. Together, these findings reveal a primary airway-to-brain sensory pathway that detects locally produced prostaglandins and mediates systemic sickness responses to respiratory virus infection.

DOI: 10.1038/s41586-023-05796-0

Source: https://www.nature.com/articles/s41586-023-05796-0