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When children with asthma get viral infections, they often land in the hospital with exacerbations that are very difficult to treat. This happens even when children are taking their controller medications, which is puzzling and frustrating to both pediatricians and parents. Now, researchers in Children's Division of Immunology have found a previously unknown biological pathway explaining why influenza induces asthma attacks—and why these attacks respond poorly to existing asthma drugs.
Studies in a mouse model, published online May 29 by Nature Immunology, reveal that influenza activates a newly recognized group of innate immune cells called natural helper cells—first discovered only recently for their role in fighting intestinal worm infections.
"Since the lung is related to the gut—both are exposed to the environment—we asked if natural helper cells might also be in the lung and be important in asthma," says Senior Investigator Dale Umetsu, MD, PhD.
Subsequent experiments showed that influenza A infection stimulates production of the cytokine IL-33, activating natural helper cells in the lung. These natural helper cells then secrete asthma-inducing compounds.
The study adds to a growing understanding of asthma as a collection of different processes, all causing airways to constrict in response to a trigger. Most asthma-control drugs, such as inhaled corticosteroids, act on the TH2 pathway, which is important in allergic asthma and has been a main focus of asthma research for the past three decades.
But targeting the TH2 pathway isn't effective against influenza-induced attacks because they are triggered by a different pathway. If drugs specifically targeting this pathway could be found, asthmatic children could be more effectively protected when they get the flu and possibly other viral infections, Dr. Umetsu says.
Moreover, Dr. Umetsu's group previously identified a third independent pathway, involving natural killer T-cells (NKT cells). In mice, NKT-cell activation alone was sufficient to cause asthma in response to exposure to ozone (a major air pollutant). Compounds targeting NKT cells are now in preclinical development.
"We need to understand the specific asthma pathways present in each individual with asthma and when they are triggered, so we can give the right treatment at the right time," Dr. Umetsu says. |
