Since the start of the coronavirus pandemic, it has been a mystery why some people fought for life after being infected, while others were completely unaware of the disease as they showed no symptoms. An international team of scientists with participation from Vienna has now identified an immune messenger as a major cause of severe disease progression and lung damage.
“The dysregulated immune response and inflammatory mechanisms leading to severe Covid-19 disease are still not fully understood. We recently identified aberrant cell death induced by ligands (binding proteins of receptors; note) as a cause of fatal inflammation. We hypothesized that this process could also cause or contribute to the pathological inflammation and lung failure following SARS-CoV-2 infection,” wrote Marie-Christine Albert (University of Cologne) and her co-authors, including Roman Reindl -Schwaighofer from the University of Cologne. University Clinic for Internal Medicine III in Vienna (MedUni/AKH), in “Cell Death and Differentiation”.
Tests with mutated virus strains on mice
First of all, the scientists developed a new animal model (MA20) with mice, with which the important disease processes of Covid-19 could be mapped. To do this, the experts used a SARS-Cov-2 virus strain with a mutation that caused the pathogen to have a stronger affinity for the ACE2 receptors in mice. ACE2 receptors are the entry points for SARS-CoV-2 into cells. In series experiments with twenty infections of new animals each, a virus was bred that caused serious to fatal diseases in the animals.
Immune messenger causes cell suicide
Finally, young and old mice of a known laboratory strain were infected. “Concurrent with the occurrence of cell death and inflammation, the expression of FasL (Fas ligands) on monocytic macrophages and NK cells (“phagocytes” and so-called natural killer cells; note) increased in the mice infected with MA20” , they wrote. Scientist. FasL is essentially an immune messenger. When FasL binds to cells with the corresponding receptor (Fas), it sends a signal that triggers programmed cell death (apoptosis), a form of cell suicide. Normally, this mechanism serves to eliminate unnecessary and potentially harmful cells in mammals and humans. However, this usually does not work with cancer cells.
Researcher: “Blocking FasL reduces cell death”
The scientists have turned things around. They blocked FasL in mice infected with SARS-CoV-2. The result: this treatment dramatically increased the animals’ lifespan, for example from 40 to 90 percent in older mice. “Therapeutic blockade of FasL reduces cell death and inflammation in the lungs of MA20-infected mice,” the scientists noted. Apparently, immune cells with a particularly strong production of Fas ligands are responsible for the often fatal pulmonary complications – caused by severe tissue damage due to cell death – in the context of Covid-19 diseases.
The highlight, according to the study authors: “FasL is also present in higher amounts in lung lavage fluid (fluid from samples taken for diagnostic purposes; note) of Covid-19 patients at a critical stage of the disease. Overall, the study results identify FasL as a determining factor (in those affected; note) of the disease-causing immune response that drives the severity and lethality of Covid-19. This implies that patients with severe Covid-19 disease could benefit from blocking FasL as a treatment.”
Source: Krone
I am an experienced and passionate journalist with a strong track record in news website reporting. I specialize in technology coverage, breaking stories on the latest developments and trends from around the world. Working for Today Times Live has given me the opportunity to write thought-provoking pieces that have caught the attention of many readers.
