Researchers at McMaster University have discovered not only how specific viral infections potentially cause tissue damage, but also how to prevent it.
When combating viral infections, such as COVID-19, researchers found how Type I interferon (IFN) prevents the immune system from “going rogue” and targeting the body’s own tissues.
On May 17th, 2022, their research was published in the journal PLOS Pathogens.
IFN is a well-known anti-viral signaling molecule secreted by the body’s cells that may activate a potent immune response against dangerous viruses, according to senior author Ali Ashkar.
What we have found is that it is also critical to stop white blood cells from releasing protease enzymes, which can damage organ tissue. It has this unique dual function to kick start an immune response against a viral infection on the one hand, as well as restrain that same response to prevent significant bystander tissue damage on the other.”
Ali Ashkar, Study Senior Author and Professor, Medicine, McMaster University
The researchers used mice to evaluate IFN’s capacity to modulate a potentially harmful immune response. Researchers used flu and the HSV-2 virus, a common sexually transmitted infection. The study also used data from COVID-19 patients in Germany, particularly post-mortem lung samples.
“For many viral infections, it is not actually the virus that causes most of the tissue damage, it is our heightened immune activation towards the virus,” stated Ashkar.
Our body’s immune response is trying to fight off the virus infection, but there’s a risk of damaging innocent healthy tissue in the process. IFNs regulates the immune response to only target tissues that are infected. By discovering the mechanisms the immune system uses that can inadvertently cause tissue damage, we can intervene during infection to prevent this damage and not necessarily have to wait until vaccines are developed to develop life-saving treatments.”
Emily Feng, Study First Co-Author and PhD Student, Department of Medicine, McMaster Immunology Research Centre, McMaster University
Amanda Lee, Study’s first co-author and a family medicine resident added, “This applies not just to COVID-19, but also other highly infectious viruses such as flu and Ebola, which can cause tremendous and often life-threatening damage to the body’s organs. This has the potential in the future to be used to alleviate virus-induced life-threatening inflammation and warrants further research.”
According to Ashkar, harmful proteases are released as a result of a “cytokine storm,” which a life-threatening inflammation is caused by viral infections. The cytokine storm has been a common cause of mortality in COVID-19 patients, although therapy has been discovered to prevent and decrease it.
Steroids like dexamethasone, according to Ashkar, are already used to control an overactive immune response to viral infections. Doxycycline, antibiotic used mostly for bacterial infections and as an anti-inflammatory medication, inhibits the activity of proteases, causing bystander tissue damage, according to scientists.
Lee, A. J., et al. (2022) Type I interferon regulates proteolysis by macrophages to prevent immunopathology following viral infection. PLOS Pathogens. doi.org/10.1371/journal.ppat.1010471.