Studying the mice, the team discovered that a small group of neurons in the airways plays a crucial role in informing the brain of a flu infection. They also observed evidence of a secondary pathway from the lungs to the brain that becomes active during infection. While most people get sick several times a year, scientific knowledge of how the brain makes us feel sick lags behind research on other bodily conditions like hunger and thirst. The article is an important first step in understanding brain-body communication during infection.

“This research helps us understand the fundamental mechanism of pathogen detection and how it relates to the nervous system, which has been largely mysterious until now,” said senior author Steven Liberles, professor of cell biology and a researcher at the HMS Blavatnik Institute. Howard Hughes Medical Institute. . The findings also shed light on how nonsteroidal anti-inflammatory drugs such as ibuprofen and aspirin relieve flu symptoms. If the results can be translated to humans, the study could have important implications for developing more effective treatments for the flu.

a contagious mood

The Liberles lab is interested in how the brain and body interact to control physiology. For example, how the brain processes sensory information from internal organs and how sensory signals can trigger or inhibit the feeling of nausea has been studied before. In a new paper, researchers turn their attention to another important type of disease that controls the brain: disease caused by a respiratory infection.

Liberles explained that during an infection, the brain controls the symptoms as the body mounts an immune response. These may include general symptoms such as fever, loss of appetite and lethargy, as well as specific symptoms such as congestion or cough in respiratory disease or vomiting or diarrhea in gastrointestinal disease. The team chose to focus on influenza, a respiratory virus that causes millions of illnesses and doctor visits and causes thousands of deaths each year in the United States.

After conducting a series of experiments on mice, first author Na-Ryum Bin, an HMS research associate in the Liberles lab, identified a small population of neurons embedded in the glossopharyngeal nerve that runs from the throat to the brain. More importantly, he discovered that these neurons are necessary to signal to the brain that a flu infection is present and have receptors for lipids called prostaglandins. These lipids are produced by both mice and humans during infection and are affected by drugs such as ibuprofen and aspirin.

Cutting the glossopharyngeal nerve, removing neurons, blocking prostaglandin receptors on these neurons, or treating mice with ibuprofen similarly reduced flu symptoms and increased survival rate. Taken together, the data show that these airway neurons detect prostaglandins produced during influenza infection and become a communication channel from the upper throat to the brain.

“We believe these neurons transmit information that a pathogen is out there and initiate the neural circuits that control the disease response,” Liberles said. Said.

The findings explain how drugs like ibuprofen and aspirin reduce flu symptoms and suggest that these drugs may even improve survival. Researchers have found evidence of another potential pathway for disease from the lungs to the brain. They found that it is activated in the second stage of infection, when the virus penetrates deeper into the respiratory tract. The team was surprised to find that this additional pathway did not involve prostaglandins. Mice in the second stage of infection did not respond to ibuprofen. According to the authors, the data reveal the possibility of improving flu treatment if scientists can develop drugs that target an additional pathway.