Publication:
Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner

dc.contributor.authorSepahi, Ali
dc.contributor.authorKraus, Aurora
dc.contributor.authorCasadei, Elisa
dc.contributor.authorJohnston, Christopher A.
dc.contributor.authorGalindo-Villegas, Jorge
dc.contributor.authorKelly, Cecelia
dc.contributor.authorGarcía-Moreno, Diana
dc.contributor.authorMuñoz, Pilar
dc.contributor.authorHuertas, Mar
dc.contributor.authorSalinas, Irene
dc.contributor.authorMulero Méndez, Victoriano Francisco
dc.contributor.departmentSanidad Animal
dc.date.accessioned2024-03-04T07:43:15Z
dc.date.available2024-03-04T07:43:15Z
dc.date.issued2019-06-03
dc.description© © 2019. Published under the PNAS license.. This document is the published version of a published work that appeared in final form in Proceedings of the National Academy of Sciences (PNAS). To access the final work, see DOI: https://www.pnas.org/doi/full/10.1073/pnas.1900083116es
dc.description.abstractThe nervous system regulates host immunity in complex ways. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with pathogens; however, OSNs’ ability to detect danger and initiate immune responses is unclear. We report that nasal delivery of rhabdoviruses induces apoptosis in crypt OSNs via the interaction of the OSN TrkA receptor with the viral glycoprotein in teleost fish. This signal results in electrical activation of neurons and very rapid proinflammatory responses in the olfactory organ (OO), but dampened inflammation in the olfactory bulb (OB). CD8α+ cells infiltrate the OO within minutes of nasal viral delivery, and TrkA blocking, but not caspase-3 blocking, abrogates this response. Infiltrating CD8α+ cells were TCRαβ T cells with a nonconventional phenotype that originated from the microvasculature surrounding the OB and not the periphery. Nasal delivery of viral glycoprotein (G protein) recapitulated the immune responses observed with the whole virus, and antibody blocking of viral G protein abrogated these responses. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviruses. These results indicate a function for OSNs as a first layer of pathogen detection in vertebrates and as orchestrators of nasal–CNS antiviral immune responses.es
dc.formatapplication/pdfes
dc.format.extent9es
dc.identifier.doihttps://doi.org/10.1073/pnas.1900083116
dc.identifier.eisbnBiological Sciences June 3, 2019 116 (25) 12428-12436es
dc.identifier.issnPrint: 0027-8424
dc.identifier.issnElectronic: 1091-6490
dc.identifier.urihttp://hdl.handle.net/10201/139879
dc.languageenges
dc.publisherNational Academy of Sciences (NAS)es
dc.relationThis work was supported by US Department of Agriculture and Food Research Initiative Grant 2DN70-2RDN7 (to I.S.), NSF Integrative Organismal Systems (IOS) Award 1755348 (to I.S. and M.H.), and NIH Centers of Biomedical Research Excellence Grant P20GM103452, as well as Spanish Ministry of Economy and Competitiveness Grants BIO2014-52655-R and BIO2017-84702-R (to V.M.), and cofunded with Fondos Europeos de Desarrollo Regional/European Regional Development Funds. C.K. was funded by the Stephanie Ruby Fellowship and NSF IOS Award 1456940 (to I.S.).es
dc.relation.publisherversionhttps://www.pnas.org/doi/full/10.1073/pnas.1900083116es
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleOlfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manneres
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
relation.isAuthorOfPublication369f9ade-8896-4d91-84c5-e3f94a526070
relation.isAuthorOfPublication.latestForDiscovery369f9ade-8896-4d91-84c5-e3f94a526070
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