Scientists at the University of New Mexico recently discovered antiviral roles in the olfactory neurons present in fish, leading to a better understanding of how neurons and immune cells work together to control viral infection, according to a group of scientists led by Irene Salinas.
Respiratory viruses — like the flu — are known to enter the nasal cavity and spread the infection to other organs in the body like the brain and the lungs.
In 2014 The Salinas Lab, a group of scientists led by Salinas, an associate professor of Biology at UNM, found rainbow trout to have a nasal immune system and developed the first nasal vaccines from fish.
The lab published a study titled, “Olfactory Sensory Neurons Mediate Ultra-Rapid Antiviral Immune Responses in TrkA-Dependent Manner” in June of this year in the Proceedings of the National Academy of Sciences. The study was funded by both the National Science Foundation (NSF) and the United States Department of Agriculture (USDA), according to UNM Newsroom.
The study shows the cross-talk between olfactory sensory neurons and the immune systems of fish.
“The thing that really popped out was all of the neuronal genes that were modulated by the virus, something we were not expecting,” Salinas said. “We all think of vaccines as something that affects the immune system, but we started to see the olfactory neurons and olfactory receptors were being modified,” she added.
Salinas compared her research to children inhaling a flu vaccine through a nasal spray, adding that no one had previously studied what happens to neurons in the human nose after receiving the vaccine.
“Our research shows that neurons are able to respond to viruses,” Salinas said. “One of the most important findings is that we cannot ignore that tissues, like the olfactory epithelium, have many different types of cells, not just immune cells.”
The lab looked at how the nose is efficient in blocking infections from reaching the brain and other organs in the body. Neurons in the nose change when a viral vaccine is delivered and how areas in the brain respond to olfactory neurons that had detected the vaccine in the periphery, she explained.
Salinas said previous research focused on the brain’s immune responses to pathogens was only conducted on certain parts of the brain when there is an active infection occurring, but not when the infection occurs elsewhere in the nervous system (in this case the nose).
The Salinas Lab could detect the virus was in the nose but the virus never made it to the brain. They found that neurons in the nose send signals to the brain, and the brain helps the nose cope with the presence of the virus.
“It was a really cool communication axis that nobody had seen before,” Salinas said. “It was like the nose was talking to the brain and the brain was talking to the nose – both of them helping each other to make the virus stay only in the nose and never progress to the brain and never cause any damage.”
One percent of cells located at the top of the nose in the fish olfactory system called crypt neurons disappeared quickly after the vaccine was delivered to the nasal cavity of the fish. Further investigation revealed that the cells were dying when the receptor they express, TrkA, interacted with the virus.
Continued research found blocking crypt neurons from dying was not enough to stop the whole immune response from going to the brain. Salinas said they predicted that there is a step in between neurons being activated and the message being sent as an electrical signal to the brain. This is absolutely necessary for the immune response to take place.
By collaborating with electrophysiologist Dr. Mar Huertas at Texas State University, the lab was able to prove that the brain is electrically activated when the virus enters the olfactory system.
Neurological responses to nasal vaccines occurred at a very fast rate — within 15 minutes. Salinas said this could be helpful in vaccine development since previously researchers would usually wait weeks to evaluate the effect of nasal vaccines on the immune system.
“Interactions between neurons and immune cells are super fast, we see it happen in a few minutes,” she said. “That’s probably one of the reasons why nasal vaccines are so effective, and we are not harnessing that aspect of the biology yet.”
Dr. Ali Sepahi, the first author of the study, said one of the most interesting aspects of the research published was that fish could smell the danger and alert the immune system immediately.
“The immune system needs to be very fast in order to be able to stop the virus from reaching the brain, where you do not want any inflammatory response,” Sepahi said.
“This type of olfactory sensory neurons (crypt neurons) was previously known for detection of sex pheromone and food, but now we see that they can smell the virus and mount the immune response. When we removed the crypt neurons in fish, we saw they were more susceptible to viral infection and therefore had a higher mortality rate compared to fish with crypt neurons,” Sephani said.
A similar type of immunity could be present in humans as well, according to Salinas. The lab is currently researching the immune system of mice to translate their findings in fish to human health.
Amanda Britt is the Photo Editor for the Daily Lobo. She can be contacted at firstname.lastname@example.org or on Twitter @AmandaBritt__