When someone gets a bad infection, the body’s immune system rushes in to fight the germs. But sometimes this defense system becomes too strong and starts hurting the person’s own tissues and organs. This condition, known as sepsis, is still one of the leading causes of death in hospitals worldwide.
Researchers have now found an important protein that normally keeps the immune response in check and prevents it from going too far. The study is published in Redox Biology.
The protein is called PP4. It works inside certain immune cells, especially macrophages and neutrophils, which are like the first responders of the body. In healthy situations, PP4 acts as a quiet regulator. It stops one immune cell from sending too many alarm signals to another. Without enough PP4, macrophages release large amounts of a signaling molecule called CCL5.
This molecule then binds to receptors on neutrophils and triggers them to create sticky, web-like traps known as NETs. While NETs can help catch bacteria, too many of them cause extra inflammation, release harmful chemicals, and damage blood vessels and organs.
To understand this process, the team created special mice that lack PP4 only in their immune cells. When these mice were given conditions that mimic severe infection, they became much sicker, showed more tissue damage, and had higher death rates compared to normal mice. The researchers observed that the missing PP4 led to uncontrolled chemical signals between macrophages and neutrophils, resulting in excessive NET formation, harmful oxygen molecules, and tissue-destroying enzymes.
Interestingly, the study also showed that blocking the receptor for CCL5 on neutrophils could calm this overreaction and reduce the damage. In lab tests with immune cells, adding back the normal working version of PP4 — but not a mutant - successfully lowered the harmful signals and prevented the creation of too many NETs.
These findings help explain why some people develop deadly sepsis while others recover. The balance controlled by PP4 appears to be a key factor in deciding whether the immune response protects or harms the body. Because PP4 naturally works to limit excessive inflammation without completely shutting down the immune system, it could become an important target for new medicines.
Scientists hope that future drugs designed to boost PP4 activity or block the harmful CCL5 pathway might help patients with severe infections. Such treatments could reduce organ damage and improve survival rates. This research highlights how understanding the fine control of our immune cells may lead to smarter ways to treat sepsis and other inflammatory diseases in the future.
“PP4 acts like a natural brake that prevents our immune system from causing friendly fire during serious infections,” says first and corresponding author Prof. Feng-Ming Yang at Graduate Institute of Physiology, National Taiwan University.
Prof. Feng-Ming Yang's email address: fmyang1024@ntu.edu.tw
To see article on Asia Research News: https://www.asiaresearchnews.com/content/discovering-new-way-stop-body-overreacting-severe-infection