{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:19:47Z","timestamp":1790849987785,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T00:00:00Z","timestamp":1601164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Type I interferon receptors are expressed by the majority of vagal C\u2010fibre neurons innervating the respiratory tract<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Interferon alpha and beta acutely and directly activate vagal C\u2010fibers in the airways.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The interferon\u2010induced activation of C\u2010fibers occurs secondary to stimulation of type 1 interferon receptors<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Type 1 interferons may contribute to the symptoms as well as the spread of respiratory viral infections by causing coughing and other defensive reflexes associated with vagal C\u2010fibre activation<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>We evaluated the ability of type I interferons to acutely activate airway vagal afferent nerve terminals in mouse lungs. Using single cell RT\u2010PCR of lung\u2010specific vagal neurons we found that IFNAR1 and IFNAR2 were expressed in 70% of the TRPV1\u2010positive neurons (a marker for vagal C\u2010fibre neurons) and 44% of TRPV1\u2010negative neurons. We employed an <jats:italic>ex vivo<\/jats:italic> vagal innervated mouse trachea\u2010lung preparation to evaluate the effect of interferons in directly activating airway nerves. Utilizing 2\u2010photon microscopy of the nodose ganglion neurons from <jats:italic>Pirt\u2010Cre;R26\u2010GCaMP6s<\/jats:italic> mice we found that applying IFN\u03b1 or IFN\u03b2 to the lungs acutely activated the majority of vagal afferent nerve terminals. When the type 1 interferon receptor, IFNAR1, was blocked with a blocking antibody the response to IFN\u03b2 was largely inhibited. The type 2 interferon, IFN\u03b3, also activated airway nerves and this was not inhibited by the IFNAR1 blocking antibody. The Janus kinase inhibitor GLPG0634 (1\u00a0\u03bc<jats:sc>m<\/jats:sc>) virtually abolished the nerve activation caused by IFN\u03b2. Consistent with the activation of vagal afferent C\u2010fibers, infusing IFN\u03b2 into the mouse trachea led to defensive breathing reflexes including apneas and gasping. These reflexes were prevented by pretreatment with an IFN type\u20101 receptor blocking antibody. Finally, using whole cell patch\u2010clamp electrophysiology of lung\u2010specific neurons we found that IFN\u03b2 (1000\u00a0U\u00a0ml<jats:sup>\u22121<\/jats:sup>) directly depolarized the membrane potential of isolated nodose neurons, in some cases beyond to action potential threshold. This acute non\u2010genomic activation of vagal sensory nerve terminals by interferons may contribute to the incessant coughing that is a hallmark of respiratory viral infections.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280276","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T06:35:52Z","timestamp":1601274952000},"page":"5541-5554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Acute activation of bronchopulmonary vagal nociceptors by type I interferons"],"prefix":"10.1113","volume":"598","author":[{"given":"Mayur J.","family":"Patil","sequence":"first","affiliation":[{"name":"The Johns Hopkins School of Medicine Departments of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Ru","sequence":"additional","affiliation":[{"name":"The Johns Hopkins School of Medicine Departments of Medicine  Baltimore 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Departments of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-5560","authenticated-orcid":false,"given":"Brendan J.","family":"Canning","sequence":"additional","affiliation":[{"name":"The Johns Hopkins School of Medicine Departments of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5299-9029","authenticated-orcid":false,"given":"Bradley J.","family":"Undem","sequence":"additional","affiliation":[{"name":"The Johns Hopkins School of Medicine Departments of Medicine  Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3055-19.2020"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1378\/chest.10-3327","article-title":"Transient receptor 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