The immunological role of crypt olfactory neurons against neurotropic viruses in teleost fish

Autor: Ali Sepahi, Aurora Kraus, Jorge Galindo-Villegas, Cecilia Kelly, Diana Garcia-Moreno, Victoriano Mulero, Mar Huertas Pau, Irene Salinas
Rok vydání: 2018
Předmět:
Zdroj: The Journal of Immunology. 200:173.15-173.15
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.200.supp.173.15
Popis: Vertebrate olfactory sensory neurons (OSNs) are located in direct contact with the external environment and therefore they directly exposed to microorganisms such as viruses. Teleost fish have four types of OSNs, including crypt neurons, a cell type with enigmatic function. Crypt neurons express tyrosine receptor kinase A (TrkA)-like molecule and ORA4. In this study, we hypothesized that TrkA expressing crypt neurons are fast sensors of viruses in the olfactory mucosa of fish serving as an ultra-rapid mechanism to elicit local antiviral immune responses. Our results show that, within minutes, nasal delivery of rhadboviruses induces caspase dependent apoptosis in crypt neurons along with neuronal activation in rainbow trout olfactory organ (OO) and olfactory bulb (OB). Induction of chemokine CCL19 and prostaglandin synthase expression was detected 15 minutes after nasal delivery of virus in OO; whereas, in parallel, significant downregulation of CCL19 expression was measured in the OB. Pharmacological blocking of TrkA abolished these responses. CD8+ T cells infiltrated the OO within minutes of nasal viral delivery and this response was abrogated when TrkA was blocked. We identified that the microvasculature surrounding the OB and not the peripheral blood is the source of the infiltrating CD8 T cells suggesting a rapid shunt of these immune cells from the OB microvasculature into the OO. In support, ablation of crypt neurons in zebrafish results in increased susceptibility to rhabdoviral challenge. Combined, our results indicate a novel function for a subset of teleost OSNs, crypt neurons, and the importance of sensory neurons as a first layer of danger detection in vertebrates.
Databáze: OpenAIRE