A protein that helps to fight viruses can also block lung damage repair

June 11, 2020

Researchers at the Francis Crick Institute have found that a protein which is initially helpful in the body's immune response to a virus, can later interfere with the repair of lung tissue. The work, published in Science, highlights the need for careful consideration regarding the use of this protein to treat viruses, including coronavirus.

When a virus infects the lungs, the body attempts to defend itself and fight off the infection. One defensive mechanism is the activation of a protein, called interferon lambda, which signals to surrounding lung tissue cells to switch on anti-viral defences.

Interferon lambda is currently being investigated in clinical trials as a potential treatment for COVID-19*, so understanding the biology underlying its anti-viral effects is important.

The research team investigated the effects of this protein in the lab and found that if it is active for an extended period, it inhibits the repair of the lung tissue. This could prolong lung damage and increase the risk of subsequent bacterial infections.

The Crick scientists observed that in mice with influenza, having increased levels of this protein in their lungs meant that their epithelial cells multiplied less. These cells make up the lining of the airspaces in the lung and need to multiply to replace damaged cells and repair damage. This was the case for mice treated with the protein experimentally and also mice that had produced the protein naturally, as a result of their response to the virus.

Furthermore, cultures of human lung epithelial cells treated with this protein were also less able to grow.

Andreas Wack, author and group leader of the Immunoregulation lab at the Crick says, "This is a really potent protein with many different functions. At the beginning of a viral infection, it is protective, triggering functions that help to fight the virus. However, if it remains in the tissue for too long, it could become harmful.

"This means, for any anti-viral treatment that uses this protein, there is a really careful balance that must be made. Clinicians should consider the timing of the treatment, the earlier this better, and the duration of treatment."

While this research studied mice infected with influenza, the effects of this protein should be similar for other viruses that also cause lung damage, including coronavirus.

The paper has been published alongside research from Harvard Medical School, which found that severe COVID-19 patients showed strong expression of this protein in their lungs.**

Jack Major, lead author and PhD student in the Immunoregulation lab at the Crick says, "Understanding how our bodies respond to infection has never been more important. Differences in our immune responses have huge implications for whether a treatment will work and what the side effects might be.

"Our results suggest that before pursuing treatment with interferon lambda, doctors should consider at what stage of the disease patients are, as treatment late in infection may increase the risk of prolonged damage."

The Crick researchers will continue to study inflammatory pathways in lung infections, including infection with coronavirus.

For further information, contact: press@crick.ac.uk or +44 (0)20 3796 5252

The Francis Crick Institute Science paper referenced in this release is entitled 'Type I and III interferons disrupt lung epithelial repair during recovery from viral infection' and will be available here https://science.sciencemag.org/lookup/doi/10.1126/science.abc2061

*Interferon lambda is being used in US clinical trial for treating COVID-19. More info here https://med.stanford.edu/news/all-news/2020/05/covid-19-drug-for-outpatients-tested.html

**The Harvard Medical School paper referenced in this release is entitled 'Type III interferons disrupt the lung epithelial barrier 1 upon viral recognition.'

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King's College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.


The Francis Crick Institute

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.