Study reveals asthma's viral trigger
For more than one in ten Australians, the cold winter months, typified by increased bouts of colds and sniffles, bring on an additional challenge: asthma attacks triggered by viral infections.
Asthmas and allergies often go hand-in-hand, and Harvard Medical School Professor Dale Umetsu says that this has led asthma researchers to focus on the immune cells that mediate the allergic response.
But, in their paper published today in Nature Immunology , Umetsu and colleagues show that the flu virus can trigger a different type of immune response. Their finding may help explain why patients who are hospitalised with severe asthma don't respond to their medication.
"TH2 cells, mast cells and eosinpophils are all [immune] cells that are related to allergy and are involved in adaptive immunity where there is memory for allergy," explains Umetsu.
These cells are found in the lungs of almost all people with asthma; notably those with allergic asthma, the most common form of asthma. They respond to corticosteroids, medication that helps limit airway inflammation and constriction and mucus secretion.
However, asthma can be triggered by factors such as air pollution and viral infection.
"These are really non-allergic problems," says Umetsu. "This lead us to investigate how viral infections cause asthma, because we didn't think it was related to allergy."
The researchers designed an experiment to measure an asthma-type feature called airway hyper-reactivity (AHR) in several mouse models. They used the methacholine challenge test, which is also used to diagnose asthma in humans.
"One of the first studies we did was to infect mice that lack the ability to mount an adaptive immune response with the influenza virus. We then challenged them with increasing amounts of a chemical called methacholine [it causes the airway muscles to spasm] and found we could get AHR," says Umetsu. "Then we began looking for other cells that might mediate this response."
Umetsu says a recent study identified a new type of immune cell called natural helper cells that are found in the gut and have a role in fighting gut parasites.
Intriguingly, these cells produced a signalling factor called interleukin 13 (IL-13) that, on its own, can bring on all the features of allergic asthma.
"We then went looking for these cells in the [mouse] lungs. They were not only present, but the numbers of these cells greatly increased following influenza infection," says Umetsu.
To prove that the natural helper cells were causing AHR in response to viral infection, the researchers carried out a series of 'deletion and reconstitution' experiments.
"We isolated these [natural helper] cells from the [mouse] lungs and transferred them to mice that lack the ability to produce IL-13 and therefore do not develop AHR when they are infected with influenza. Sure enough, when these cells were in situ , the IL-13 knockout mice developed AHR."
Umetsu's team then confirmed the importance of the natural helper cells in asthma, by giving the mice that could not mount an adaptive immune response an antibody that blocked natural helper cells, which prevented the viral-induced AHR.
'Hot new field' of research
Umetsu says it may take a couple of years before they know whether these natural helper cells are also present in the lungs of people with asthma.
"This is a hot new field. Everybody is excited about these immune cells that, until one or two years ago, no one knew existed," says Professor Charles Mackay of Monash University , Melbourne.
"This paper also potentially answers questions around the heterogeneity of people with asthma, including reasons why some don't respond to treatment with corticosteroids, says Mackay.
According to Umetsu, the experiments to test whether the natural helper cells are steroid-resistant are underway. They also plan to study whether other viral infections can cause asthma.
"This is the first virus we have looked at, we plan to study others, but there are only certain viruses that one can look at in mice," he adds.