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
  • Animals
  • Apoptosis
  • CD8-Positive T-Lymphocytes/immunology*
  • Caspase 3/metabolism
  • Infectious hematopoietic necrosis virus/immunology*
  • Nasal Mucosa/immunology
  • Nasal Mucosa/virology
  • Olfactory Receptor Neurons/cytology
  • Olfactory Receptor Neurons/physiology*
  • Olfactory Receptor Neurons/virology
  • Oncorhynchus mykiss
  • Receptor, trkA/metabolism*
(all 12)
PubMed
31160464 Full text @ Proc. Natl. Acad. Sci. USA
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
Figures
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
c264Tg/+; ums4Tg/+chemical treatment by environment: metronidazoleProtruding-mouth
c264Tg/+; ums4Tg/+chemical treatment by environment: metronidazoleDay 5
c264Tg/+; ums4Tg/+chemical treatment by environment: metronidazoleDay 5
c264Tg/+; ums4Tg/+chemical treatment by environment: metronidazole, viral treatment by exposure to environment: Sprivivirus cyprinusDays 7-13
c264Tg/+; ums4Tg/+viral treatment by exposure to environment: Sprivivirus cyprinusDays 7-13
1 - 5 of 5
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c264TgTransgenic Insertion
    ums4TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      Fish
      c264Tg/+; ums4Tg/+
      1 - 1 of 1
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      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      GAL4EFGGAL4
      mCherryEFGmCherry
      NTREFGNTR
      1 - 4 of 4
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      Mapping
      No data available
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      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.