Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
The School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Cell. 2024 Oct 17;187(21):5981-5997.e14. doi: 10.1016/j.cell.2024.08.009. Epub 2024 Sep 6.
Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11MrgprA3) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.
打喷嚏和咳嗽是许多呼吸道病毒感染和过敏的主要症状。一般认为，打喷嚏和咳嗽涉及共同的感觉受体和分子神经传递机制。在这里，我们表明，鼻黏膜由几个离散的感觉神经元群支配，但只有一个神经元群（MrgprC11MrgprA3）介导对多种鼻刺激物、过敏原和病毒的打喷嚏反应。尽管这个神经元群也支配气管，但它不会介导咳嗽，这是我们新建立的咳嗽模型所揭示的。相反，一个不同的感觉神经元群（生长抑素[SST]）介导咳嗽而不是打喷嚏，揭示了打喷嚏和咳嗽之间意想不到的感觉差异。在电路水平上，打喷嚏和咳嗽信号通过不同的神经通路进行传递和调节。总之，我们的研究揭示了打喷嚏和咳嗽之间感觉受体和神经传递/调节机制的差异，为呼吸道病毒感染和过敏的症状管理提供了神经元药物靶点。
