Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner

Sepahi, A.; Kraus, A.; Johnston, C. A.; Galindo-Villegas, J.; Kelly, C.; Garcia-Moreno, D.; Munoz, P.; Mulero, V.; Huertas, M.; Salinas, I.

doi:10.1101/464214

bioRxiv · 10.1101/464214

Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner

Sepahi, A.·Kraus, A.·Johnston, C. A.·Galindo-Villegas, J.·Kelly, C.·Garcia-Moreno, D.·Munoz, P.·Mulero, V.·Huertas, M.·Salinas, I.

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Abstract

The nervous system is known to regulate host immune responses. However, the ability of neurons to detect danger and initiate immune responses at barrier tissues is unclear. Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with the external environment and therefore directly exposed to pathogens. Here, we report that nasal delivery of rhadboviruses induced apoptosis in crypt OSNs in rainbow trout olfactory organ (OO) via the interaction of the OSN TrkA receptor with viral glycoprotein. This signal resulted in pro-inflammatory responses in the OO and dampened inflammation in the olfactory bulb (OB). CD8+ cells infiltrated the OO within minutes of nasal viral delivery and this response was abrogated when TrkA was blocked. Infiltrating CD8+ cells originated from the microvasculature surrounding the OB and not the periphery. Ablation of crypt neurons in zebrafish resulted in increased susceptibility to rhabdoviral challenge. Our results, therefore, indicate a novel function for OSNs as a first layer of pathogen detection in vertebrates.

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Sepahi, A., Kraus, A., Johnston, C. A., Galindo-Villegas, J., Kelly, C., Garcia-Moreno, D., Munoz, P., Mulero, V., Huertas, M., Salinas, I.. 2018-11-06. Olfactory sensory neurons mediate ultra-rapid antiviral immune responses in teleosts in a TrkA-dependent manner. https://doi.org/10.1101/464214

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