'Double agent' in the immune system may make us vulnerable to bacterial infections

October 4, 2018, The Scripps Research Institute
Credit: CC0 Public Domain

Scientists at Scripps Research have discovered the role of an immune system double agent. This molecule, called USP18, can help curtail immune responses, but it can also open the door to bacterial infections, such as harmful listeria and staph infections.

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

The researchers found that deleting the specific gene for this protein in certain helps the body fight bacterial infections.This work, conducted in mouse models, offers a potential antimicrobial approach that could target both bacteria and viruses.

It all comes down to type 1 interferons, a type of immune molecule produced at the start of a viral . Interferons fight off the virus, and then their levels should drop when the threat is gone.

Study senior author John Teijaro, Ph.D., assistant professor at Scripps Research, says scientists have long wanted to understand a paradox in immunology—the question of how interferon-stimulated genes (ISGs) that usually help against viruses also dampen the host's ability to resist many bacterial infections.

For the new study, the team found that deleting a single ISG known as Usp18 in mouse dendritic cells, a type of immune cell, enhanced the body's ability to control infections with two strains of Gram-positive bacteria. They also found that normal induction of USP18 after infection impaired antibacterial responses mediated by a protein called and accompanying reactive oxygen species generation, which help destroy bacteria in cells.

"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," says Teijaro.

Teijaro emphasizes that the study is basic biology—it illuminates the fundamental workings of the immune system—but it's worth investigating whether USP18 can be targeted with drug therapies to treat bacterial infections. Knowing how to inhibit USP18 function could also give doctors the tools to boost interferon activity to better fight viral infections as well.

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

There's one more potential advantage to developing therapies targeting USP18, Shaabani says. "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."

Explore further: Cell death protein also damps inflammation

More information: Namir Shaabani et al, The probacterial effect of type I interferon signaling requires its own negative regulator USP18, Science Immunology (2018). DOI: 10.1126/sciimmunol.aau2125

Related Stories

Cell death protein also damps inflammation

October 1, 2018
Inflammation is one strategy your body uses to fight infection, but if it gets out of control it can kill instead of heal. In the Sept. 18 issue of Immunity, UConn Health immunologist Vijay Rathinam and colleagues show how ...

Novel infection fighter

June 15, 2018
Hospital-acquired infections are a serious threat to patient lives, especially with the rise of antibiotic-resistant bacteria. One drug that may prove helpful in the fight against these infections is monophosphoryl Lipid ...

Immune cell study prompts rethink on how to tackle infections

February 14, 2017
Fresh insights into how immune cells are regulated could signal a new approach to tackling infections.

Single gene links susceptibility to rare infections with predisposition to autoimmune disease

October 13, 2014
The mutations were familiar, but the patients' conditions seemed baffling at first. A team lead by Rockefeller University researchers had linked variations in an immune gene to rare bacterial infections. Shortly afterward, ...

Possible treatments identified for highly contagious stomach virus

January 14, 2015
Antibiotics aren't supposed to be effective against viruses. But new evidence in mice suggests antibiotics may help fight norovirus, a highly contagious gastrointestinal virus, report scientists at Washington University School ...

Scientists identify 'first responders' to bacterial invasion

October 23, 2017
When bacteria enter our body, they kick-start a powerful immune response. But this chain of reactions doesn't fully account for our immediate responses. Researchers at KU Leuven, Belgium, show that so-called ion channels ...

Recommended for you

A bad influence—the interplay between tumor cells and immune cells

October 16, 2018
Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ...

New immunotherapy targeting blood-clotting protein

October 15, 2018
Normally, the blood protein fibrin does not enter the brain. But in several neurological disorders, the blood-brain barrier—which keeps large molecules in the blood from entering the brain—becomes abnormally permeable, ...

Function of neutrophils during tumor progression unraveled

October 15, 2018
Researchers at The Wistar Institute have characterized the function of neutrophils, a type of white blood cells, during early stages of tumor progression, showing that they migrate from the bone marrow to distant sites and ...

Immune health maintained by meticulously ordered DNA

October 15, 2018
Walter and Eliza Hall Institute researchers have revealed how immune health is maintained by the exquisite organisation skills of a protein called Pax5.

Enzyme that triggers autoimmune responses from T-cells in patients with MS found

October 11, 2018
A team of researchers from Switzerland, the U.S. and Spain has isolated an enzyme that triggers an autoimmune response from T-cells in patients with MS. In their paper published in the journal Science Translational Medicine, ...

Scientists reveal new cystic fibrosis treatments work best in inflamed airways

October 11, 2018
A new UNC School of Medicine study shows that two cystic fibrosis (CF) drugs aimed at correcting the defected CFTR protein seem to be more effective when a patient's airway is inflamed. This is the first study to evaluate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.