An airway-to-brain sensory pathway mediates influenza-induced sickness.
An airway-to-brain sensory pathway mediates influenza-induced sickness.
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通风到脑的感觉途径介导了流感引起的疾病。
DOI：
10.1038/s41586-023-05796-0
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发表时间：
2023-03
期刊：
影响因子：
64.8
通讯作者：
Liberles, Stephen D.
中科院分区：
文献类型：
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作者：
Bin, Na-Ryum;Prescott, Sara L.;Horio, Nao;Wang, Yandan;Chiu, Isaac M.;Liberles, Stephen D.
病原体感染引起一种刻板的疾病状态，涉及神经组织的行为和生理变化。在感染时，免疫细胞释放一场细胞因子和其他介质的“风暴”，其中许多被神经元检测到；然而，在自然感染期间引起疾病行为的神经回路和神经免疫相互作用机制仍不清楚。阿司匹林和布洛芬等非处方药被广泛用于缓解疾病，并通过阻断前列腺素E2 （PGE2）的合成发挥作用。一个主要的模型是PGE2穿过血脑屏障，直接作用于下丘脑神经元。在这里，使用广泛覆盖外周感觉神经元图谱的遗传工具，我们确定了一小群检测pge2的舌咽部感觉神经元（岩盐GABRA1神经元），它们对小鼠流感诱导的疾病行为至关重要。切除岩膜GABRA1神经元或靶向敲除这些神经元中的PGE2受体3 (EP3)，可消除流感引起的早期感染期间食物摄入量、水摄入量和活动能力的减少，并提高存活率。遗传引导解剖图谱显示，岩状GABRA1神经元在感染后投射到鼻咽粘膜区域，环氧化酶-2表达增加，并在脑干中表现出特定的轴突靶向模式。总之，这些发现揭示了一个主要的气道到大脑的感觉途径，检测局部产生的前列腺素并介导呼吸道病毒感染的全身性疾病反应。一小群前列腺素e2应答的舌咽部感觉神经元提供了气道和脑干之间的感觉通路，介导对早期流感病毒感染的疾病反应。
Pathogen infection causes a stereotyped state of sickness that involves neuronally orchestrated behavioural and physiological changes. On infection, immune cells release a ‘storm’ of cytokines and other mediators, many of which are detected by neurons; 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) synthesis. A leading model is that PGE2 crosses the blood–brain barrier and directly engages hypothalamic neurons. 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. A small population of prostaglandin E2-responsive glossopharyngeal sensory neurons provides a sensory pathway between airway and brainstem that mediates sickness responses to early-phase influenza virus infection.
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影响因子：
64.8
作者：
Horio N;Liberles SD
通讯作者：
Liberles SD
DOI：
10.1016/s1098-3597(01)90069-9
发表时间：
2001-01-01
期刊：
Clinical cornerstone
影响因子：
--
作者：
Green, G A
通讯作者：
Green, G A
DOI：
10.1111/j.1749-6632.1998.tb08321.x
发表时间：
1998-01-01
期刊：
MOLECULAR MECHANISMS OF FEVER
影响因子：
--
作者：
Dantzer, R;Bluthé, RM;Kelley, KW
通讯作者：
Kelley, KW
影响因子：
8.8
作者：
Kupari, Jussi;Haring, Martin;Ernfors, Patrik
通讯作者：
Ernfors, Patrik
刺激性室室核向AGRP神经元电路，驱动饥饿。
影响因子：
64.8
作者：
通讯作者：
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