Scientists discover unknown antiviral defense that acts before innate immune system

By John Murphy, MDLinx
Published December 1, 2015

Key Takeaways

Scientists have discovered a previously unknown antiviral defense mechanism that goes into action even before the innate immune system—the body’s first line of defense. This discovery likely explains why people aren’t always sick despite ever-present viruses and bacteria, according to a study published online November 30, 2015 in the journal Nature Immunology.

“Our study fundamentally alters our understanding of how the body begins its defense against viruses,” said co-lead investigator Søren Riis Paludan, PhD, Professor in the Department of Biomedicine at Aarhus University, in Aarhus, Denmark.

He added, “This can help to explain how we can be constantly exposed to the viruses and bacteria that always surround us without activating the entire immune system every time, something that would lead to more frequent influenza-like symptoms.”

Up to this point, immunology researchers believed that interferons constituted the innate immune system’s first line of defense against viral infection. But the newly discovered immune reaction takes place on a smaller, local scale. When the early defense mechanism detects the presence of a virus at the mucosal surface, it reacts with a rapid and low-grade influx of neutrophils with antiviral activity into the tissue—it’s a skirmish, not a battle.

“We do not yet know the precise significance of this [early] mechanism, but it may explain why some people become more ill from viral infections such as influenza than others. The same may apply to other viral infections that are initiated on mucous membranes such as HIV and herpes,” Dr. Paludan said.

If this early immune reaction fails to suppress the virus, the virus invades and infects the body. This in turn triggers the innate immune system’s reaction that involves interferon, which fights the virus, but can also lead to excessive inflammation and symptoms of sickness. 

In this investigation, Dr. Paludan and researchers at eight other sites in the U.S. and Europe sought to characterize this early reaction by infecting wild type mice with herpes simplex virus (HSV). The next day, they analyzed mRNA samples from the mice and found certain chemokines—the kind that are normally induced through inflammatory signaling pathways.

They also found a high amount of neutrophils, which appeared to be recruited by the chemokines as an antiviral defense. However, they found no interferon reaction until the second day.

All these functions indicate that this early defense mechanism occurs at the mucosal surface before the innate immune response begins, the researchers concluded.

“We will now begin to map out the molecules that are involved. Once we have done this, it will be possible to identify people with defects in the mechanism, just as there is a potential to develop new forms of treatment,” Dr. Paludan said. “At the same time, the mechanism may turn out to have significance also for non-viral diseases, so continued research into this area shows great potential.”

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