A new study has found an unidentified immune response inside the nose that can explain why people are more likely to develop Colds, Flu and COVID-19 during the winter season.

There is evidence that colder weather suppresses an immune response inside the nose, explaining why colds, the flu, and COVID-19 are more common in the winter months.

This is the first scientific mechanism that explains why viruses such as the common cold, flu, and COVID-19 are more prone to spread during colder seasons.

Researchers at Mass Eye and Ear and Northeastern University have uncovered an immune response that defends against upper respiratory infection-causing viruses within the nose. Further research found that cooler temperatures impair this defensive response, increasing the likelihood of an infection.

According to the scientists, the new research provides the first scientific basis to explain why viruses like the common cold, the flu, and COVID-19 are more likely to surge in colder seasons. It was published today in The Journal of Allergy and Clinical Immunology.

“Conventionally, it was thought that cold and flu season occurred in cooler months because people are stuck indoors more where airborne viruses could spread more easily,” explains senior author Benjamin S. Bleier. “Our study however points to a biological root cause for the seasonal variation in upper respiratory viral infections we see each year, most recently demonstrated throughout the COVID-19 pandemic.”

The nose is an opening between the body and the external world, making it vulnerable to infection. Pathogens can be breathed in or put directly (by the hands, for example) into the front of the nose, where they infect cells as they move backwards through the airway and into the body. This can lead to an upper respiratory infection. No one has known for a long time how the airway protects itself from these pathogens.

That is, until research conducted in 2018 under the direction of Dr. Bleier and Mansoor Amiji, PhD, Distinguished Professor of Pharmaceutical Sciences at Northeastern University, revealed an innate immune response brought on when bacterium is breathed via the nose: Extracellular vesicles, also known as exosomes, are microscopic fluid-filled sacs that are released into the mucus by cells at the front of the nose in order to surround and kill germs. These cells first identify the bacteria.

According to Dr. Bleier, releasing this EV swarm is like “kicking a hornets’ nest.”

The 2018 research also demonstrated how the EVs transport antibiotic proteins that shield other cells from bacteria before it enters the body too deeply via the mucus from the front of the nose to the rear of the airway.

The goal of the current study was to find out if viruses that cause some of the most prevalent upper respiratory illnesses may also cause this immune response when they are breathed via the nose.

The researchers, led by the first study’s author Di Huang, PhD, a research fellow at Mass Eye and Ear and Northeastern, looked at how cells and samples of nasal tissue from surgery patients and healthy volunteers responded to three viruses: one coronavirus and two rhinoviruses that cause the common cold.

They discovered that the nasal cells responded to each virus by sending out a swarm of EVs, but that this response employed a different signaling mechanism than that used to combat bacteria. The researchers also found out how the body responds to viruses. When the EVs were released, they acted as decoys because they carried receptors that the virus would bind to instead of the nasal cells.

Dr. Huang adds: “the more decoys, the more the EVs can mop up the viruses in the mucus before the viruses have a chance to bind to the nasal cells,” thereby suppressing the infection.

The researchers then looked at how this response changed when it was colder. This is important for nasal immunity because the temperature inside the nose depends a lot on the temperature of the air it breathes in. The temperature within the nose dropped by roughly 5 degrees Celsius when they subjected healthy participants from a room temperature setting to temperatures of 4.4 degrees Celsius (39.9 degrees Fahrenheit) for 15 minutes. They next applied this drop in temperature to samples of nasal tissue and saw a weakened immunological response. The nasal cells released 42% fewer EVs and their antiviral proteins were compromised.

“Combined, these findings,” according to Dr. Huang, “provide a mechanistic explanation for the seasonal variation in upper respiratory infections.”

In the future, scientists will try to find out if the same thing happens with other pathogens.

“We’ve uncovered a new immune mechanism in the nose that is constantly being bombarded, and have shown what compromises this protection,” adds Dr. Amiji. “The question now changes to, ‘How can we exploit this natural phenomenon and recreate a defensive mechanism in the nose and boost this protection, especially in colder months?’”

Source: 10.1016/j.jaci.2022.09.037

Image Credit: Getty


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