Why does a short-term lung infection cause long-term lung damage?

The deadliest time in viral respiratory diseases is sometimes after the virus is cleared from the body
.

Researchers at Washington University School of Medicine in St.
Louis have found clues about how lung damage develops after respiratory infections
.

"Vaccines, antiviral drugs, and antibody therapies are all helpful, but they are not a solution for those who are already in the advanced stage of the disease," senior author, Selma and Herman Selding Professor of Medicine, Cell Said Michael J.
Holtzman, MD, professor of biology and physiology
.

It has long been recognized that acute respiratory infections can cause chronic lung disease
.

As part of this research, Holtzman and his colleagues, including the first author and medical lecturer Dr.
Kangyun Wu, studied mice infected with Sendai virus
.

The researchers examined the lung tissues of mice infected with Sendai virus for 12 days and 21 days, and compared the samples with lung tissues of uninfected mice
.

Further experiments showed that this process depends on the protein IL-33
.

In order to evaluate the role of IL-33 in lung injury after the virus, the researchers genetically modified mice to make them lack IL-33 in the basis of lung stem cells
.
Then, the scientists infected these mice with Sendai virus, as well as another group of unmodified mice
.
These two groups of mice were equally effective in repelling the initial Sendai virus infection
.
But after three weeks of infection, the lungs of mice lacking IL-33 showed less cell overgrowth, mucus, and inflammation, indicating that they had fewer signs of harmful lung changes
.
After 7 weeks of infection, mice without IL-33 in their basal cells also had higher blood oxygen levels and lower airway hyperresponsiveness, both of which are signs of improvement in chronic lung disease
.

Holtzman said: "These results are very happy, because the removal of IL-33 and the loss of basal stem cells may make the situation worse
.
" "These transgenic mice may have died because they are no longer able to The virus repairs damage to the lung barrier normally
.
But this is not the case
.
On the contrary, mice lacking this basal cell have better results
.
This is where we are excited
.
These findings have found a cure for us to correct the bad behavior of basal stem cells.
Laid a solid foundation
.
"

A broad-based and effective therapy targeting the pathway between IL-33 and basal cell activation to prevent or treat various viruses or other forms of damage caused by lung diseases in the human lungs and other sites to meet the outside world, Holtzman said
.

"The lungs have a fairly fixed response to damage, including viral damage," Holtzman said
.
"The specific type of virus, the host’s genes, the severity of the initial disease, all these factors will affect the outcome, but it’s just a matter of degree
.
You can still see the same key factors in different situations, that’s why we believe we can There is a common treatment strategy
.
We have a drug discovery project to find such a common strategy, and this research fits this point
.
"

DOI 10.
1172 / JCI149336

Basal-epithelial stem cells cross an alarmin checkpoint for post-viral lung disease