Scientists identify “footprints of death” that can aid immune cleanup—and may be exploited by influenza

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La Trobe University researchers say dying cells can leave behind a residue containing newly identified extracellular vesicles that help direct immune clearance, but laboratory experiments suggest influenza viruses may also use the vesicles to help spread.

Researchers at La Trobe University report they have identified a previously unknown step in the cell-death process in which dying cells leave behind a residue they call a “footprint of death.” According to the team, this residue contains a newly described type of extracellular vesicle, dubbed FOOD-derived apoptotic extracellular vesicles, or F-ApoEVs, which remain at the site where a cell dies and can help guide immune cells to clear cellular debris.

The findings were published in Nature Communications. The research was led by PhD candidate Stephanie Rutter in the laboratory of Professor Ivan Poon at the La Trobe Institute for Molecular Science.

In laboratory experiments using influenza-infected cells, the researchers found viral particles could hide inside the F-ApoEVs, a mechanism the team says could potentially allow infection to spread to neighboring cells while remaining concealed within the body’s normal cleanup process.

Poon said the work suggests cell fragmentation during programmed cell death is more complex and organized than previously believed, and could point to future treatment strategies that better support immune clearance. Rutter said the study highlights how dead-cell debris is normally removed to reduce inflammation and autoimmune disease risk—including conditions such as systemic lupus erythematosus—and that the team did not expect viruses to be able to take advantage of the same process.

The study’s co-leader, Dr. Georgia Atkin-Smith of the Walter and Eliza Hall Institute of Medical Research (WEHI), said the results indicate dying cells may continue to signal to the immune system after death in ways that can affect immune function.

La Trobe University said the project involved scientists from its Research Centre for Extracellular Vesicles, the La Trobe Institute for Molecular Science, and the School of Agriculture, Biomedicine and Environment, and was conducted in collaboration with researchers at WEHI and Toronto Metropolitan University in Canada. The team said the discovery could ultimately improve understanding of both infectious disease and autoimmune disorders, though the findings are based on laboratory observations and further research will be needed to determine how the process operates in living organisms and disease settings.

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