The human immune system is incredibly complex. Scientists studying its function have discovered that a group of proteins that have been used for billions of years by bacterial organisms as a defense against pathogens are also in humans, in more complex versions. Those human proteins also help defend us from infectious invaders. The findings have suggested that some components of our immune system may have originated in early life forms, and they are now being used in new ways. The research has been reported in Science.
In this study, the researchers focused on proteins called gasdermins, which are involved in a process called pyroptosis, one mechanism used by the immune system to destroy diseased or infected cells. Gasdermins are known to rip holes in the membranes of cells that are cancerous or infected with a pathogen. Cells with torn membranes will die, and in humans, they leak molecules called cytokines, which trigger inflammation and draw the attention of the immune system.
"Pyroptosis represents one of the fastest ways that the innate immune system responds to potential threats," explained co-first study author, Alex Johnson, Ph.D., of the Dana-Farber Cancer Institute.
The human genome carries six genes that encode for gasdermins, which are active at various levels in different types of cells.
Senior study author Philip Kranzusch, Ph.D., of Dana-Farber has identified other connections between the human immune system and bacteria. Kranzusch and colleagues found that a signaling pathway in human immunity called cGAS-STING first arose in bacteria. It helps the human body detect cancer and infection. Then, the researchers wanted to find other links between "immune-related proteins in human and bacterial cells," Kranzusch said.
Bacteriophages (phages) are viruses that infect bacterial cells. There are clusters of bacterial genes called antiphage defense islands, and they help prevent phages from infecting bacteria. In this work, the researchers analyzed these regions. The work revealed 50 bacterial genes that could potentially lead to proteins that are similar to mammalian gasdermin proteins.
These proteins are widespread in common bacteria, and they have structural similarities to mammalian gasdermins, noted Johnson. The bacterial proteins are about half the size as the human versions, and in bacteria they are building blocks that make holes in membranes that are bigger than those made in human cells. Those bacterial cells simply die. But in humans, there is a much more complex cascade of downstream events when pyroptosis occurs; the immune system gets involved to protect the body.
The primitive system in bacteria "has been adapted and expanded" in humans "with regulatory systems that enable our bodies to respond to infection or cancer," said Kranzusch.