According to a new study, when mice lacking key adaptive immune cells were infected with the COVID-19 Although they were unable to clear the virus, they developed no symptoms, revealing that the body's inflammatory immune response to fight the infection was causing the condition.
The results of research were published in Science Advances.
Covid19: here's what new research has revealed
Although the inflammatory response of adaptive immune cells, such as B and T lymphocytes, clears the body of the virus, it also causes the characteristic symptoms of Covid19.
The results of the study “Adaptive Immune Cells are Necessary for SARS-CoV-2-owned Pathology”, published on January 3 in Science Advances, also indicate a potential treatment against the effects of the virus.
“Unlike other major respiratory viruses that circulate, without the adaptive immune response, Covid19 on its own does not appear to cause damage that leads to significant pathology,” said Avery August, professor of immunology at the College. of Veterinary Medicine (CVM) and vice dean. August and Hector Aguilar-Carreño, professor of virology, also at CVM, are corresponding authors of the study.
“It means we can explore therapies that modulate the immune response, so we can dampen those parts that cause inflammation while leaving intact those parts that are important for clearing the virus,” August said.
In the study, the researchers used a strain of Covid19 that has been adapted to infect mice, as strains that infect humans do not transmit well to mice. The approach allowed the study authors to directly infect a variety of engineered laboratory mice lacking elements of their immune system, including mice that do not produce B or T cells, which would otherwise recognize and respond to pathogens.
In a normal course of infection, mice begin to lose weight around day three or four and continue to do so until day seven, when many mice are often euthanized after excessive weight loss, but some survive, depending on the their viral load. The scientists monitored the amount of infection in their lungs, in part to make sure they were actually infected.
They also examined lung tissues for indications of a robust immune response, such as the presence of B and T cells and other inflammatory immune cells, and for cytokines, signaling proteins that direct immune cells to a site of infection and are associated with inflammation.
The team's initial hypothesis was that mice without B and T cells would exhibit severe symptoms and be unable to handle Covid19 infection. For example, when the same engineered mice were infected with mouse-adapted influenza, they had to be euthanized due to severe weight loss with no immune cells to protect them.
“We were very surprised when it turned out that [i topi infettati da SARS-CoV-2] they didn't lose weight, they didn't have any symptoms or conditions,” August said. At the same time, normal laboratory mice (called wild mice) used as controls showed symptoms characteristic of Covid19, including the collection of immune cells in the lungs and an inflammatory response to clear the virus.
When infections in the genetically modified mice continued for 30 days, they still showed no weight loss, behavioral changes or inflammation in the tissues.
August, Aguilar-Carreño and colleagues also tried an intermediate approach by infecting mice that had B cells but lacked most T cells, and these were also less affected by the Covid19 strain.
“Without B or T cells, the virus can replicate, but it doesn't cause any damage, because the damage is caused specifically by the adaptive immune system,” August said.
Furthermore, the researchers used genetically modified mice that specifically lacked a protein important for T cell activation, and those mice were also somewhat protected from Covid19 symptoms.
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