The 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. neuroimmunology | olfactory sensory neurons | teleost | viral immunity | TrkA

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(+)- and (-)-petromyroxol [(+)-1 and (-)-1, respectively], two novel tetrahydrofuran (THF)-diol fatty acid enantiomers, were isolated from water conditioned with larval sea lamprey. We herein describe their isolation and subsequent resolution using chiral chromatography. The absolute configuration of each enantiomer was determined by a combination of Mosher ester analysis and comparison with related natural and synthetic products. Electro-olfactogram (EOG) assays indicated that (+)-petromyroxol (1) possesses potent olfactory activity for sea lamprey.

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