Olfactory detection of viruses shapes brain immunity and behavior in zebrafish.
Aurora KrausBenjamin GarciaJie MaKristian J HerreraHanna ZwakaRoy HarpazRyan Y WongFlorian EngertIrene SalinasPublished in: bioRxiv : the preprint server for biology (2023)
Olfactory sensory neurons (OSNs) are constantly exposed to pathogens, including viruses. However, serious brain infection via the olfactory route rarely occurs. When OSNs detect a virus, they coordinate local antiviral immune responses to stop virus progression to the brain. Despite effective immune control in the olfactory periphery, pathogen-triggered neuronal signals reach the CNS via the olfactory bulb (OB). We hypothesized that neuronal detection of a virus by OSNs initiates neuroimmune responses in the OB that prevent pathogen invasion. Using zebrafish ( Danio rerio ) as a model, we demonstrate viral-specific neuronal activation of OSNs projecting into the OB, indicating that OSNs are electrically activated by viruses. Further, behavioral changes are seen in both adult and larval zebrafish after viral exposure. By profiling the transcription of single cells in the OB after OSNs are exposed to virus, we found that both microglia and neurons enter a protective state. Microglia and macrophage populations in the OB respond within minutes of nasal viral delivery followed decreased expression of neuronal differentiation factors and enrichment of genes in the neuropeptide signaling pathway in neuronal clusters. Pituitary adenylate-cyclase-activating polypeptide ( pacap ), a known antimicrobial, was especially enriched in a neuronal cluster. We confirm that PACAP is antiviral in vitro and that PACAP expression increases in the OB 1 day post-viral treatment. Our work reveals how encounters with viruses in the olfactory periphery shape the vertebrate brain by inducing antimicrobial programs in neurons and by altering host behavior.
Keyphrases
- cerebral ischemia
- signaling pathway
- resting state
- sars cov
- white matter
- subarachnoid hemorrhage
- poor prognosis
- blood brain barrier
- spinal cord
- brain injury
- induced apoptosis
- immune response
- functional connectivity
- staphylococcus aureus
- genetic diversity
- neuropathic pain
- multiple sclerosis
- binding protein
- epithelial mesenchymal transition
- public health
- pi k akt
- transcription factor
- multidrug resistant
- dendritic cells
- long non coding rna
- candida albicans
- cell migration
- oxidative stress
- drosophila melanogaster
- antimicrobial resistance