The fibers of the vagus nerve have many crucial roles. The vagus nerve helps regulate many physical functions including controlling heart rate and speech; it is related to the feeling of satiety after eating; and can modulate inflammation, for just a few examples. Now, scientists have also found that cells in the vagus nerve can help defend against damage caused when the immune system overreacts to a flu infection. These cells are known as TRPV1 vagal nociceptors and they are known to trigger coughing that can expel irritants, mucus, and foreign invaders from the lungs. But when a flu infection is occurring, these cells take on additional roles, according to a new study reported in Science Immunology.
This study used a mouse model to show that neuronal cells called TRPV1 vagal nociceptors can tamp down the immune response during a flu infection. While immune responses have to be strong enough to eliminate an infection, they can spiral out of control to cause serious damage. These TRPV1 neurons seem to offer protection against that potential damage.
"Our research shows that the infected lung is a battleground where nerves and immune cells engage in a delicate dance to safeguard our health," said co-senior study author Isaac Chiu, a professor in the Blavatnik Institute at Harvard Medical School (HMS). "Understanding this powerful neuroimmune signaling axis will be increasingly important as we design better ways to prevent and treat immune mediated damage in viral infections, which can sometimes be worse than the direct damage caused by the virus itself."
This mechanism may help explain why certain flu patients end up with chronic lung damage caused by the immune system, while others can fully recover from their infection.
In this study, the investigators utilized mice that did not express TRPV1 neurons, and infected them with flu. These mice became far sicker than flu-exposed mice that still expressed those neurons. The flu virus levels were comparable in both groups of mice, but those lacking TRPV1 neurons had more inflammation, lung damage, and death.
The mice without TRPV1 neurons also had excess immune cells called macrophages and neutrophils; these cells can cause harm when there are too many of them in tissues. Interferon immune signaling was also disrupted in these animals.
More work will be necessary to confirm these findings in humans, ands to understand exactly how TRPV1 neurons are controlling immune cells. But the research will continue.
"The vagus nerve is powerfully controlling inflammation, but how it does so remains a mystery to be solved," Chiu said. "But we're excited that it plays such a strong role in viral infections."
These findings may eventually help lead to better treatments for flu or other viral infections.
"Imagine if you could harness this brake to control inflammation in the lungs and beyond," Chiu suggested. "By stimulating related circuits where the vagus nerve shuts down immune cells, one could envision treating immune-mediated dysfunction of many kinds, including that caused by viral infections."
Sources: Harvard Medical School, Science Immunology
