Our immune systems kick into gear when we have an infection, and there are a variety of processes used by the body to eliminate pathogenic invaders. Inflammation is a normal part of the immune response; it's characterized by heat, swelling, and itching as the immune system responds to an infection. But inflammation can be a problem when it's out of control, and the immune system has to be carefully regulated so it doesn't start harming normal tissues in the body. Sepsis can arise when the immune response is too excessive, and organs are damaged. The World Health Organization has estimated that sepsis contributes to the deaths of around 11 million people every year, worldwide.
Now scientists have learned more about the biological mechanisms that underlie this process. The findings have shown that a kind of cellular message that is sent during sepsis can lead to lethal problems. This work, which may help researchers find more effective treatments for sepsis, have been reported in Cell.
As cells become infected with a pathogen, they can sense that problem and enter into programmed cell death, killing themselves off to save healthy tissue. This is done when a protein called gasdermin-D is sent to the infected cell's surface. Gasdermin proteins can link together on the surface to form a pore, and once that hole has formed in the cell's membrane, the contents of the cell leak out, and it dies.
However, these cells can also release the portion of membrane carrying the gasdermin pore. Once the hole is removed, the cell repairs the rip where the pore has been released, and the cell survives the process. The bit of membrane that has been released then forms what is known as an extracellular vesicle, which is a little sac that in this case, is now carrying the gasdermin pore around.
When the free-floating gasdermin pore, in its vesicle, reaches another cell, that gasdermin pore can then form a hole in that newly encountered cell, killing that cell. Infected cells can then not only go on to survive, but kill other cells that may not be infected. These spreading signals and increasing numbers of dead cells fuel sepsis.
Now, the researchers want to find a way to halt this process, and reduce the number of gasdermin-D vesicles in an effort to treat sepsis more effectively.
Sources: University of Connecticut, Cell
