A team of researchers from Imperial College London, University of Liège, and several other institutes have a novel pathway within the immune system that triggers an asthma attack. The study, “Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation,” appears in the journal Nature Medicine. Marie Toussaint is the first author.
Asthma is one of the most common inflammatory diseases of the airways and its incidence is increasing throughout the world. It is estimated that 10% of adults in developed countries have asthma, and the morbility of asthma is even higher. For example, in the US alone, over 25 million people suffer from asthma, and approximately 7 million of them are children.
Asthma is characterized by recurring periods of wheezing, shortness of breath, reversible airflow obstruction, and bronchospasm. Severity of the disease varies among patients. Sometimes, asthma can be life-threatening, so an appropriate treatment is essential. Asthma is a result of interaction between genetic and environmental effects. Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Some studies have linked amplification of the type-2 immune response to asthma excerbation. However, the precise mechanism of how virus infection promotes type-2 immune response remains elusive.
Now the new study reveals a novel pathway involved in asthma. Existing drugs are available to inhibit this pathway. These drugs may be repurposed to treat asthma.
Our bodies have two types of immune responses: type 1 responds to viruses and type 2 responds to allergens. In theory, activation of one should inhibit the other. However in fact, people who get a cold have increased risk of having an asthma attack. In this work, the researchers examined nasal samples from people with asthma and healthy volunteers. Results showed that asthma patients had elevated levels of proteins associated with type 2 immune response after rhinovirus infection. Moreover, they also had higher levels of host dsDNA.
Using a mouse model of allergic airway hypersensitivity, they researchers found that rhinovirus infection triggers release of dsDNA by neutrophils, a type of while blood cells that form part of the innate immune system. Further experiments in mice showed that treatment with an enzyme that degrades DNA reduced type-2 immune response after rhinovirus infection, and resulted in decreased inflammation. The enzyme, called DNase, is already used to treat cystic fibrosis.
Taken together, the study shows that extracellular dsDNA may "contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations." (Cusabio offers various proteins and antibodies. http://www.cusabio.com/)