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Human Immune System Uses Ancient Family Of Cell Death Proteins

The human immune system, that marvel of complexity, subtlety, and sophistication, includes a billion-year-old family of proteins used by bacteria to defend themselves against viruses, scientists at Dana-Farber Cancer Institute and in Israel have discovered, ScienceDaily reported.


Photo Insert: The human immune system



The findings, published online by the journal Science, are the latest in a growing body of evidence that components of our immune system -- as advanced a shield against disease as exists on the planet -- evolved early in ancient forms of life.


The study shows the immune system absorbed already existing elements and, over eons of evolution, put them to use in novel ways to meet the requirements of creatures as biologically complicated as human beings.



"There has been a tremendous amount of work by researchers around the world to understand how the human immune system functions," says the study's senior author, Dr. Philip Kranzusch, of Dana-Farber.


"The discovery that key parts of human immunity are shared in bacteria provides a new blueprint for research in this area." The proteins at the center of the study are known as gasdermins. When a cell becomes infected or turns cancerous, gasdermins form pores that punch holes in its membrane, causing it to die.


Substances known as inflammatory cytokines leak from the holes and signal the presence of infection or cancer and prompting the immune system to rally to the body's defense.


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This process, called pyroptosis, is one facet of the immune system's repertoire for killing diseased or infected cells. It complements the better-known process of apoptosis, in which crippled or infected cells self-destruct after being damaged.


"Pyroptosis represents one of the fastest ways that the innate immune system [the body's first line of defense against pathogens] responds to potential threats," says the new study's co-first author, Alex Johnson, PhD, of Dana-Farber. The human genome holds the code for six gasdermin proteins, which are expressed at varying levels in different cell types. For the current study, Johnson and his colleagues explored whether the ancestors of any of these proteins existed in bacteria.


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They had good reason for thinking they might. In 2019, Kranzusch and his colleagues found that a human immune signaling pathway called cGAS-STING, which senses abnormalities linked to cancer and infection, originated in bacteria.


"This and other discoveries motivated us to look for additional connections between immune-related proteins in human and bacterial cells," Kranzusch notes.


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Co-first author Dr. Tanita Wein, co-senior author Dr. Rotem Sorek, and colleagues at the Weizmann Institute of Science, in Israel, analyzed sections of bacterial DNA known as "antiphage defense islands" because they contain clusters of genes that protect bacteria from infection by viruses known as phages. They identified 50 bacterial genes predicted to give rise to proteins whose structure was similar to that of gasdermin proteins in mammals.



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