From olfaction to immunity: Characterization of nasal immunity in bony fish

The olfactory system is a common route pathogen entry in vertebrates. As a consequence, the nasopharynx-associated lymphoid tissue (NALT) needs to rapidly clear infections without compromising the sense of olfaction. NALT is present in teleost fish but its cellular and molecular mechanisms of action have not been investigated to this date. This dissertation focuses on three aims: 1. investigating the role of CCL19-like as a primordial chemokine in vertebrate nasal immunity, 2. determining the presence of tissue microenvironments within the olfactory organ (OO) of rainbow trout, and 3. understanding the immune contributions of olfactory sensory neurons (OSNs) in teleosts against viruses. In aim 1, we report six isoforms of CCL19-like chemokine in salmonids such as CK12. CK12 is mainly expressed in mucosal tissues and plays an important role in antiviral immunity. Although recombinant protein CK12 is not chemotactic in vitro, it induces infiltration of APCs and CD8+ T cells into OO of rainbow trout in vivo. In aim 2, we demonstrate the presence of two different microenvironments (mucosal tip and neuroepithelial) in the OO of rainbow trout. The tip of the epithelium harbors clusters of CD8α+ cells whereas few numbers are found in the neuroepithelium. CD8a+ cell localization corresponds with a higher expression of chemokine and chemokine receptors in the tip versus the neuroepithelial side. We report that cell proliferation in response to viral nasal delivery occurs mainly at the tip. In aim 3, we unravel for the first time a new function for OSNs by which nasal rhadboviruses induce apoptosis in crypt neurons, a type of OSN, in rainbow trout via the interaction of viral G glycoprotein and the neuron TrkA receptor. CD8α+ T cells infiltrate to the OO within minutes of nasal viral delivery and this response was abrogated when TrkA was blocked. Infiltrating CD8α+ T cells originated from the microvasculature surrounding the olfactory bulb (OB) and not the periphery. In conclusion, this dissertation provides the first tissue, cellular and molecular characterization of teleost NALT and reveals a novel function of vertebrate OSNs in eliciting rapid nasal anti-viral immune responses in the OO and OB