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How influenza drives asthma

Specialized cells of the innate immune system, identified in the lungs for the first time, play a central role in virus-induced asthma

By | May 29, 2011

Viral respiratory infection causes severe asthma attacks in almost all patients with asthma -- a reaction classically attributed to T cells of the adaptive immune system. Now, scientists have identified a pathway in mice by which a subset of innate immune cells, found in mammalian lungs for the first time, orchestrate influenza-induced asthma.
Influenza A virus
Source: linkurl:CDC;http://www.cdc.gov/h1n1flu/images.htm?s_cid=cs_001
The discovery, published online today in linkurl:Nature Immunology,;http://www.nature.com/ni/index.html suggests the innate immune system, and not just the adaptive immune system, triggers asthma attacks after viral infections. The cells, plus a newly identified pathway by which the cells are activated, could provide novel targets for therapies to control viral-induced asthma attacks, which fail to respond to conventional asthma medications, the authors write. The research is "fresh and engaging," said linkurl:Gary Anderson,;http://www.pharmacology.unimelb.edu.au/research/LungDisease.html who studies lung disease at the University of Melbourne in Australia and wasn't involved in the research, in an email. But, he warns, its medical relevance is unclear as drugs targeting the pathway identified have not succeeded in clinical trials of asthma. At Children's Hospital at Harvard Medical School, immunologist linkurl:Dale Umetsu;http://www.hms.harvard.edu/dms/immunology/fac/Umetsu.html and colleagues examined a mouse model of asthma induced with influenza virus, and were surprised to see an asthma reaction within five days. "Normally, the adaptive immune response takes 10 to 14 days," said Umetsu. "But with influenza, the responses occurred so fast that it couldn't really involve adaptive immunity and T cells." They then challenged mice lacking T and B cells -- both involved in adaptive immunity -- with influenza virus, and still recorded an asthmatic reaction, confirming the attacks were not caused by an adaptive immune response. Measuring the cytokine secretions in the lungs of infected mice -- molecules that signal immune cells to the site of an infection --the team identified two that were being secreted in large quantities and contributing to the lung inflammation, interleukin 33 and interleukin 13. The cytokines led the team to a population of innate immune cells activated by interleukin 33, called natural helper cells, which then secrete large amounts of interleukin 13. These cells are known to be essential in immune response to helminth infection in the intestines, but "this is the first study to find and characterize this substrate in the lungs," said first author Ya-Jen Chang. New therapies are greatly needed for patients with viral-induced asthma attacks, who often end up in the hospital, said Umetsu. "Now that we've found these innate lymphocytes involved in asthma, we think they can be a good target for therapeutic applications," added Chang. Yet drugs targeting the interleukin 13 pathway have essentially failed in clinical trials of asthma, said Anderson. This, however, may reinforce the idea that multiple pathways cause asthma, and even if researchers find a drug that successfully targets one pathway, effective treatments may require a combination of therapies. Y. Chang, et al., "Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity," Nat Immun, doi: 10.1038/ni.2045, 2011.
**__Related stories:__***linkurl:Top 7 in dermatology;http://www.the-scientist.com/news/display/57850/
[1st December 2010] *linkurl:Antiviral response promotes bacterial infection;http://www.the-scientist.com/news/display/25036/
[10th October 2006] *linkurl:The Innate Immunity Adaptor List Grows;http://www.the-scientist.com/2005/07/18/18/1/
[18th July 2005]
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Comments

Avatar of: Mike Waldrep

Mike Waldrep

Posts: 155

May 31, 2011

Interesting! I hope that everyone had a nice Memorial Day!
Avatar of: barbara vincent

barbara vincent

Posts: 9

May 31, 2011

As an asthmatic who ends up in hospital with pneumonia and asthma whenever I suffer a viral infection such as influenza, this is great news. I have often thought that there must be some other process involved. However, since receiving shots for influenza each year, this has dramatically improved and I have not had influenza for several years now and consequently, no hospital stays due to it.
Avatar of: Ed Rybicki

Ed Rybicki

Posts: 82

June 1, 2011

I have watched a couple members of my family go from viral respiratory infections through to persistent asthma-like irritable airway syndrome recently - and find myself wondering if viruses other than influenza don't in fact trigger asthma de novo, rather than exacerbating existing conditions?\n\nAnd to the previous commenter: most of the world does not celebrate Memorial Day.

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