Dead cells disrupt normal immune responses

Scientists at the University of Sheffield have revealed that cells which are programmed to die, a process known as apoptosis, can disrupt the normal function of immune cells, called macrophages. This can impact on how well they respond to wounds and patrol the body to seek out infection.

Macrophages are needed at wound sites to prevent infection and to aid healing processes, but these white blood cells can also cause and worsen many human diseases, including cancer, heart disease and neurodegenerative disorders. The Sheffield scientists have now shown that immune cells prioritise the clearance of dead cells, which overrides their normal migration to sites of injury and impairs immune responses. Their work has been published in the journal PLOS Biology.

“Billions of cells die within our bodies on a daily basis and many of these are removed and digested by our immune cells,” said study co-author Dr Iwan Evans. “If this removal process goes wrong, it can lead to damaging autoimmune conditions. Excessive or inappropriate immune responses worsen or cause a very broad range of human diseases, from cancer to neurodegeneration.”

Macrophages at a wound site. Image credit: University of Sheffield.

The research to investigate the interactions between dying cells and immune cells was conducted using fruit flies which contain macrophage-like cells highly similar to our own immune cells. The study also uncovered a novel role for a protein called Six-Microns-Under (or Simu) in keeping immune cells at sites of injury. Without this protein, the macrophages left wound sites precociously.

“The study shows that the way fruit fly blood cells respond to injuries and dying cells is even more similar to how our own immune cells respond than previously thought,” said study co-author Hannah Roddie.

“We are now looking into what signals macrophages use to track down dying cells and how they choose between the dead cells and wounds. We’re fascinated to understand how immune cells are kept at the sites of injuries.”

The study gives scientists new insights into the mechanisms that control immune cells within our bodies, such as how they get to and are kept at sites of injuries. It could also help pave the way for new therapies to manipulate these cells and accelerate healing processes.

Top image caption: Fruit fly macrophages responding to a wound in the presence of apoptosis. Image credit: University of Sheffield.

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