Published in Nature Communications, the study sheds new light on what happens when cells die and are removed from the body.

The research was led by PhD candidate Stephanie Rutter in the laboratory of Professor Ivan Poon at the La Trobe Institute for Molecular Science (LIMS). The team found that the steps involved in cell death are far more organized and important than scientists previously realized.

Newly Discovered Cell Death Vesicles

As cells reach the end of their life cycle and begin to self-destruct, they undergo a series of physical changes. The researchers observed that dying cells alter their shape, detach from nearby structures, and leave behind a residue they call “the footprint of death.”

Within this residue, the team discovered a previously unknown type of Extracellular Vesicle (EV).

EVs are microscopic particles released by cells that carry proteins, lipids, DNA and RNA to other cells. They play an essential role in cell-to-cell communication throughout the body.

The newly identified vesicles, called F-ApoEVs, remain at the site where a cell has died. They act like breadcrumb trails that help the immune system locate and remove cellular debris before it can trigger unwanted inflammation.

How Viruses Exploit the Cleanup Process

The researchers also uncovered an unexpected twist.

In laboratory experiments involving influenza-infected cells, they found that viruses could take advantage of this natural cleanup mechanism. Viral particles were able to hide inside the F-ApoEVs, potentially allowing infection to spread to neighboring cells while remaining concealed within the body’s normal disposal process.

Professor Poon, Director of the Research Centre for Extracellular Vesicles (RCEV), said the findings may have important implications for future therapies.

“Understanding this basic biological process could open new avenues of research to develop new treatments that harness these steps and help the immune system better fight disease,” Professor Poon said.

“Billions of cells are programmed to die each day as a part of normal turnover and disease progression, and until now, it was believed that the cell fragmentation process during cell death was random and fairly simple.

“Our findings demonstrate the complexity of this process and highlight how each step in the process is actually critical to help the dying cell break down efficiently and to be cleared away by the immune system.”

Cell Communication After Death

Lead researcher and PhD candidate Stephanie Rutter said the findings highlight the importance of communication between cells and show how viruses can manipulate these biological systems.

“We know that the body clears away dead cell fragments to prevent them lingering and causing inflammation and autoimmune diseases such as Systemic Lupus Erythematosis (SLE), and we saw F-ApoEVs are readily cleared from the site of cell death,” Stephanie said.

“What we didn’t expect was how viruses can also take advantage of this process and cause infection by hiding in F-ApoEVs.”

The team believes the discovery could eventually improve understanding of both infectious diseases and autoimmune disorders, leading to new treatment strategies.

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

New Insights Into Immune Function

Study co-leader Dr. Georgia Atkin-Smith of WEHI said understanding how dying cells communicate with the immune system is important because cell death plays a role in a wide range of diseases.

“This study has revealed that dying cells can continue to communicate from the grave and may impact immune function,” Dr. Atkin-Smith said.

The research was carried out by scientists from La Trobe University’s RCEV, LIMS and the School of Agriculture, Biomedicine and Environment (SABE). The project was conducted in collaboration with researchers at WEHI and Toronto Metropolitan University in Canada.