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 have discovered.
The findings, published 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 that 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. “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, signaling the presence of infection or cancer and prompting the immune system to rally to the body’s defense.
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.
The human genome holds the code for six gasdermin proteins, which are expressed at varying levels in different cell types. For the current study, the authors explored whether the ancestors of any of these proteins existed in bacteria.
They had good reason for thinking they might. In 2019, the researchers 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,” the senior author notes.
The authors 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.
“I determined a series of structures of these proteins using X-ray crystallography, which confirmed at atomic detail their architectural similarity with mammalian gasdermins,” the lead author relates. The types of bacteria that harbor these proteins are widespread, living in soil, leaves, and other natural habitats.
The structural work showed that while human and bacterial gasdermins are structurally alike, the bacterial versions tend to be about half as big, yet serve as building blocks for membrane pores larger than those seen in humans. All these gasdermins are activated by a similar mechanism, but the chain of events they set in motion is far more extensive in human cells. In bacterial cells, viral infection may trigger cells to die from punctured membranes, stopping viruses in their tracks. In human cells, the death of an infected cell triggers a cascade of events that brings other elements of the immune system to bear on the infection.
“This is an example of a very primitive form of defense, which, in humans, has been adapted and expanded with regulatory systems that enable our bodies to respond to infection or cancer,” the senior author says.
The discovery of traces of a primitive form of immunity within the staggering complexity of the human immune system can help researchers better understand how the system came to be. “Seeing the simplest version of a machine can give you a new level of understanding of the machine as a whole,” the author remarks. “The same principle can apply to research into the immune system.”
https://www.science.org/doi/10.1126/science.abj8432
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fbacterial-gasdermins&filter=22
Human immune family of cell death proteins also found in bacteria
- 1,567 views
- Added
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Developing more accurate measure of body fat
Read more
Very high levels of 'good' cholesterol may be harmful
Read more
A new inhibitory kind of neurons found in human brain
Read more
Resetting brain function in psychosis with cannabis extract
Read more
Aspirin does not show lower risk of first cardiovascular event
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar