With this year’s severe flu season, one statistic is especially chilling. Each year, around 50% of all children under age 5 years who die from the flu were previously healthy, according to the CDC. Adults who die from the flu, on the other hand, typically had a medical condition that increased their risk of mortality. A new study published in the Journal of Immunology offers new insights as to why healthy children are much more vulnerable. It also opens new opportunities for treatment.

“We found that in young, healthy mice the immune system overreacted to the influenza virus, which led to more inflammation, greater lung damage, and increased mortality compared to healthy adults exposed to the virus,” says lead author Bria Coates, MD?, critical care physician at Ann & Robert H. Lurie Children’s Hospital of Chicago and assistant professor of pediatrics at Northwestern University Feinberg School of Medicine. “This new evidence reverses earlier assumptions that the young are more susceptible to the flu because their immune systems do not mount a strong enough response to the virus. In our study, juvenile mice continued to have an exaggerated immune response even after the virus was cleared from the body. The flu was a trigger to the inflammation that their system couldn’t turn off, which proved fatal.”

The study examined specific immune pathways known to be activated during flu infections in both humans and mice, which makes the findings relevant to children. Coates and colleagues focused on the initial immune response to the flu, using healthy adult and young mice who have not had previous exposures to the virus. They discovered that in the young, more immune cells called monocytes were recruited to the lungs, and that the gene expression profiles of these cells had more inflammatory features, causing greater inflammation and more severe lung injury.

“Our findings provide new targets for developing effective medicines to treat the flu in children,” says Coates. “We can seek ways to prevent monocytes from coming to the lungs, or we can target monocyte behavior in the lungs to reduce dangerous inflammation.”

Since these targeted treatments are not yet available, Coates stresses that flu vaccination is crucial. “Even when the vaccine is not a perfect match to the circulating influenza strain, as is the case this year, the vaccine still helps prevent more severe infections if children get sick with the flu,” she says.