‘Footprint of death’ gives new clues to cell life and disease spread

Scientists at La Trobe University have discovered a previously unknown way for viruses to spread throughout the body, potentially paving the way for the development of more effective drugs. Study, published V Natural communicationsopens up new understanding of the process of cell death and renewal.

Under the guidance of Ph.D. candidate Stephanie Rutter in Professor Ivan Poon's laboratory at the La Trobe Institute of Molecular Sciences (LIMS), the research shows how important each step in the process is to help a dying cell break down and be eliminated from the body. immune system.

The researchers found that as cells self-destruct, they change shape, break away from their environment, and leave behind a residue called a “death trail,” which contains a previously undetected type of extracellular vesicles (EVs).

EVs are tiny packets secreted by cells to transport proteins, lipids, DNA and RNA to other cells, serving as an essential mechanism for communication between cells.

The new EVs, known as F-ApoEVs, mark the site of a dead cell and serve as clues to help the immune system identify and clear cell fragments, preventing unwanted inflammation.

But early tests on cells also showed that when dying cells become infected with influenza, the virus can disrupt the clearance process by hiding particles inside F-ApoEV, which can allow the infection to spread to neighboring cells.

Professor Poon, director of the Research Center for Extracellular Vesicles (RCEV), said the findings could have a major impact on future drug development.

“Understanding this basic biology could open up new research opportunities to develop new treatments that take advantage of these steps and help the immune system better fight disease,” Professor Poon said.

“Billions of cells are programmed to die every day as part of normal renewal and disease progressionand until now it was believed that the process of cell fragmentation during cell death is random and rather simple.

“Our results demonstrate the complexity of this process and highlight that each step in the process is truly important to help dying cells effectively break down and be cleared by the immune system.”

Leading researcher and Ph.D. candidate Rutter said the research demonstrated the importance of intercellular communication in maintaining health and how viruses can manipulate these processes.

“We know that the body clears out dead cell fragments so they don’t linger and cause inflammation and autoimmune diseases such as systemic lupus erythematosus (SLE), and we saw that F-ApoEVs are readily cleared from the site of cell death,” Rutter said.

“What we didn't expect was that viruses could also take advantage of this process and cause infection by hiding in F-ApoEV.”

Researchers hope this discovery could lead to better understanding and ultimately more effective treatments for infectious and autoimmune diseases.

“The more we understand about cell death and what happens to cells after they die, the better we can understand disease pathologies and find new treatments,” Rutter said.

Study co-leader Dr Georgia Atkin-Smith from WEHI said understanding how dying cells interact within the immune system is critical given the widespread implications cell death for many diseases.

“This study shows that dying cells can continue to communicate even from beyond the grave and can influence immune function,” Dr Atkin-Smith said.