PUBLICATION
Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner
- Authors
- Sepahi, A., Kraus, A., Casadei, E., Johnston, C.A., Galindo-Villegas, J., Kelly, C., García-Moreno, D., Muñoz, P., Mulero, V., Huertas, M., Salinas, I.
- ID
- ZDB-PUB-190605-6
- Date
- 2019
- Source
- Proceedings of the National Academy of Sciences of the United States of America 116(25): 12428-12436 (Journal)
- Registered Authors
- Galindo-Villegas, Jorge, Mulero, Victor
- Keywords
- TrkA, neuroimmunology, olfactory sensory neurons, teleost, viral immunity
- MeSH Terms
-
- Apoptosis
- CD8-Positive T-Lymphocytes/immunology*
- Receptor, trkA/metabolism*
- Infectious hematopoietic necrosis virus/immunology*
- Oncorhynchus mykiss
- Nasal Mucosa/immunology
- Nasal Mucosa/virology
- Caspase 3/metabolism
- Olfactory Receptor Neurons/cytology
- Olfactory Receptor Neurons/physiology*
- Olfactory Receptor Neurons/virology
- Animals
- PubMed
- 31160464 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Sepahi, A., Kraus, A., Casadei, E., Johnston, C.A., Galindo-Villegas, J., Kelly, C., García-Moreno, D., Muñoz, P., Mulero, V., Huertas, M., Salinas, I. (2019) Olfactory sensory neurons mediate ultrarapid antiviral immune responses in a TrkA-dependent manner. Proceedings of the National Academy of Sciences of the United States of America. 116(25):12428-12436.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping