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Alexa F. Ciesinski, Ashley Moseman, Dorian B. McGavern
The olfactory epithelium not only plays a crucial role as a physiological barrier between the environment and the central nervous system (CNS), but it also acts as an immune barrier to prevent potential viral, bacterial, and fungal CNS invasion. Due to their anatomical placement, olfactory sensory neurons (OSNs) are uniquely vulnerable to infection, and therefore complex local innate and adaptive immune responses are necessary to protect the CNS from potential airborne dangers. Neurotropic viruses, such as vesicular stomatitis virus, (VSV) can readily infect OSNs. Little is known, however, about the protective mechanisms in place to prevent viral spread from the OSNs into the CNS.
This study seeks to elucidate how neuronal-immune cooperation, specifically neuronal-CTL (cytotoxic lymphocytes) interactions, contributes to viral control at the level of OSNs. Following intranasal infection of VSV, we observed the innate and adaptive CD8 T-cell responses to infection in the olfactory epithelium where the cell body of the OSNs reside and in the olfactory bulb, where their axons terminate in the glomeruli. Utilizing a novel technique, we isolated an OSN population to analyze them for specific cell markers and to understand disease progression. We found that OSNs have the capability to express MHC I, allowing them to engage in complex interactions with viral-specific CD8 T-cells. Using two-photon microscopy and T-cell motility analysis, we observed a decrease in viral-specific T-cell velocity in the presence of virally-infected OSNs. This study provides a gateway into investigating the olfactory epithelium as a crucial immune defense site. The development of this unique technique for flow cytometry will allow for further analysis of this key barrier cell, provide a better understanding of viral clearance, and allow for the development of new treatments for infection.
Last Modified November 26, 2013