Tuesday February 16, 2021
Formation of ACE receptors
How Sars-CoV-2 takes advantage of the immune system
An infection with Sars-CoV-2 is mild in the majority of those infected. But for some, the infection becomes a life-threatening condition. Researchers from Berlin now provide an explanation of why this sometimes happens.
Researchers from Berlin have observed how Sars-CoV-2 uses a defense mechanism of the immune system to increasingly attack the body’s mucous membrane cells and multiply there. Julian Heuberger’s team from the Charité University Hospital in Berlin was able to identify a messenger substance that is used by Sars-CoV-2 and converted into its opposite. “With this we can possibly provide part of the explanation why in some people the immune system has difficulty regulating or even defeating the infection,” says Heuberger according to a message of the Max Delbrück Center for Molecular Medicine (MDC), which was also involved in the investigation.
Usually the body’s defense system is a highly effective, complex interplay of various processes. So-called T cells play a key role in this. On the one hand, they render virus-infected cells harmless and, on the other hand, they release messenger substances to call for support from other immune cells. One of these messenger substances is the so-called interferon gamma, referred to as IFN-ƴ for short.
ACE receptors in mucosal cells
In addition to the immune cells, the body’s mucous membrane cells also respond to IFN-ƴ. Overall, they develop more ACE2 receptors. This in turn needs Sars-CoV-2 as a portal of entry into the cells. Infected cells in turn produce more ACE2, at the same time more IFN-ƴ is produced. This sets in motion a vicious circle in the body that promotes the spread of the viruses, thus the infection and negatively affects the course of Covid-19.
The researchers used intestinal cells to observe these reactions of the immune system. They first cultivated cells from the large intestine and turned them into a kind of organoid, a small organ in the Petri dish. Then these organoids, not even the size of a pin, were treated with IFN-ƴ and finally infected with Sars-CoV-2. Using a special microscope, the researchers were then able to measure increased ACE2 expression and demonstrate increased virus production.
The Results of the study, which were recently published in the journal “EMBO Molecular Medicine”, could carry the idea of a treatment approach for severe Covid-19 courses. “One possible strategy could be to balance the IFN-ƴ response with drugs,” explains Heuberger. However, the mechanisms on which the IFN-ƴ response is based must first be analyzed very carefully.