OCT 11, 2018 1:34 PM PDT

Revealing a 'Double Agent' in the Immune System

WRITTEN BY: Carmen Leitch

Researchers are becoming more interested in enhancing our natural defenses to fight a variety of health problems more effectively. In new work that investigated how our immune system controls microbial infections, scientists have discovered how a molecule called USP18 can help regulate immune signaling. They found that USP18 keeps the immune response under control but paradoxically, can also make us vulnerable to additional infection. The findings have been reported in Science Immunology.

Image credit: Public Domain Files

"I call the molecule a wolf in sheep's clothing," said the co-first author of the study Namir Shaabani, Ph.D., a postdoctoral researcher at Scripps Research.

At the initial stage of a viral infection, the immune system utilizes a type of molecule called a type 1 interferon to combat the virus. After the invading virus is under control, levels of type 1 interferon go down. In this study, scientists aimed to learn more about why interferon-stimulated genes (ISGs) that encourage the immune system to fight viruses also dampen the infected host’s ability to fight off infections in the first place, explained the senior author of the work John Teijaro, Ph.D., assistant professor at Scripps Research.

One such ISG is USP18. When researchers deleted the USP18 gene from a type of immune cell in a mouse model, they found that the ability to fight off infection from two different kinds of Gram-positive bacteria was enhanced.

When USP18 was activated under normal circumstances, the antimicrobial responses of mice were impaired. The team found that USP18 had this effect by inhibiting a protein called tumor necrosis factor (TNF), which allows the bacteria to reproduce. Disruption of USP18 had an antimicrobial effect; TNF function was restored and it encouraged the creation of reactive oxygen species, which can destroy bacteria.

"Our results were unexpected because the absence of USP18 augments type 1 interferon signaling, which, if the current thinking is correct, should promote rather than prevent bacterial infection," said Teijaro.

The researchers suggest that this work could open up new therapeutic avenues for bacterial and viral infections.

This is an investigation of basic processes in biology, but Teijaro noted that it provides insight into fundamental parts of the immune system, while offering new therapeutic opportunities. If USP18 function can be inhibited at the right time, it may boost the effectiveness of our natural interferons to fight microbial infections successfully. Learn more about how the immune system works from the video.

"One of our goals going forward is to test this therapeutically," said Teijaro. "We also want to expand our investigation to understand the role of USP18 in secondary bacterial pneumonia and tuberculosis infections."

There may be an important advantage to developing drugs that act upon USP18, Shaabani added. "Therapies targeting USP18 would also have the advantage of targeting the host, and not the bacteria directly, and therefore should be less susceptible to antibiotic resistance."

 

Sources: Science Daily via Scripps Research Institute, Science Immunology

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 09, 2021
Genetics & Genomics
Middle Eastern Data Fills in Some Knowledge Gaps on Human Genetics
AUG 09, 2021
Middle Eastern Data Fills in Some Knowledge Gaps on Human Genetics
Although the human genome has basically the same genes from one person to the next, there is a huge amount of variation ...
AUG 18, 2021
Cell & Molecular Biology
Insight Into an Antiviral Enzyme That Can Impact Cancer Cells
AUG 18, 2021
Insight Into an Antiviral Enzyme That Can Impact Cancer Cells
For many years, researchers have studied how an enzyme called APOBEC3 can help protect the body from pathogenic viruses, ...
SEP 06, 2021
Cell & Molecular Biology
Researchers Miniaturize the CRISPR Gene Editing Tool
SEP 06, 2021
Researchers Miniaturize the CRISPR Gene Editing Tool
The CRISPR gene editor uses RNA molecules that act as guides that ta Cas9 proteins, which are like enzymatic scissors, t ...
SEP 19, 2021
Genetics & Genomics
A New Understanding of Japanese History Through Genetics
SEP 19, 2021
A New Understanding of Japanese History Through Genetics
Palaeoarchaeologists, human geographers, and other scientists have sought to understand the evolution of humans, their c ...
SEP 24, 2021
Genetics & Genomics
Kleefstra Syndrome Reversed in Mouse Model After Birth
SEP 24, 2021
Kleefstra Syndrome Reversed in Mouse Model After Birth
Kleefstra syndrome is a rare genetic disease caused by a mutation or deletion in one copy of a gene called EHMT1, which ...
SEP 24, 2021
Cell & Molecular Biology
A Human Embryo Model is Made From Stem Cells
SEP 24, 2021
A Human Embryo Model is Made From Stem Cells
This photo by Sozen & Jorgensen et al., Nature Communications, shows an embryo-like structure made from human stem cells ...
Loading Comments...