Innate immune system protein provides a new target in war against bacterial infections

July 2, 2012

Research led by St. Jude Children's Research Hospital scientists has identified a possible new approach to defeating bacterial infections by targeting an innate immune system component in a bid to invigorate the immune response.

In this study, researchers demonstrated that the primary function of one of the innate immune molecules is to suppress inflammation, which in turn dampens the immune response to infections and other threats. Investigators showed the protein works by inhibiting two pathways that control production of specialized molecules that fight infections. The findings appear in the current online edition of the scientific journal Nature.

"The beauty of this finding is that if we can generate monoclonal against this protein, we can block . This discovery offers a completely new approach to fighting infections by targeting the host immune response rather than the ," said Thirumala-Devi Kanneganti, Ph.D., an associate member of the St. Jude Department of , and the study's senior and corresponding author. Monoclonal are laboratory-produced versions of and are designed to detect specific proteins. Kanneganti laboratory is already working to develop a neutralizing antibody.

Despite the availability of antibiotics, bacterial infections continue to extract a heavy toll of suffering and death. A better understanding of how the immune system recognizes and responds to would aid efforts to develop new, more effective treatments.

This study builds on earlier work from Kanneganti's laboratory and focuses on the NOD-like receptor protein 6 (NLRP6). NLRP6 belongs to a family of proteins that are part of the innate immune response that serves as the first line of defense. These proteins serve as sentinels working inside cells to recognize and response to infectious agents. Until now, however, nothing was known about NLRP6's role in the process.

Working in mice with and without the Nlrp6 gene, researchers tracked the immune response to different bacteria agents. This study focused on the innate immune response to Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. All are bacteria that spread through food with potentially deadly results.

Surprisingly, mice without NLRP6 were far more likely to survive infection with lethal doses of the bacteria than their normal counterparts. The NLRP6-deficient mice had fewer bacteria in their livers and spleens one and three days after infection. They also had higher than normal levels of monocytes and neutrophils in circulation. Those are white blood cells known to play an important early role in combating infections. The findings suggest that mice lacking NLRP6 mount a more effective immune response.

Researchers went on to show that NLRP6 suppressed activity in pathways that trigger production of proteins called cytokines, which promote inflammation to combat the infection. The results show that NLRP6 regulates the nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) pathways.

"The result was entirely unexpected," said Paras Anand, Ph.D., a postdoctoral fellow in Kanneganti's laboratory and the study's first author. "This is the first member from the NLR family of proteins that inhibits rather than activates pathways involved in the ."

"NLRP6 might represent an entirely new subclass of these NLR proteins that functions to impede bacterial clearance," he said. Investigators are now studying the protein's response to other infectious agents.

Previous work on this molecule demonstrated that NLRP6 also helps to limit colitis and colon cancer. Kanneganti said the findings underscore the importance of balance to a properly functioning immune system. "This molecule helps maintain a balance between promoting and suppressing inflammation. In Colitis, NLRP6 seems to protect the host from the consequences of chronic inflammation and in the other we show it impedes bacterial clearance," she said.

Explore further: Signaling molecule identified as essential for maintaining a balanced immune response

Related Stories

Signaling molecule identified as essential for maintaining a balanced immune response

July 26, 2011
(Medical Xpress) -- St. Jude Children’s Research Hospital investigators have identified a signaling molecule that functions like a factory supervisor to ensure that the right mix of specialized T cells is available to ...

Tumor suppressor protein is a key regulator of immune response and balance

July 18, 2011
St. Jude Children's Research Hospital scientists have identified a key immune system regulator, a protein that serves as a gatekeeper in the white blood cells that produce the "troops" to battle specific infections.

Immune system malfunction may trigger inflammatory bowel disease

May 13, 2011
In a finding that could have implications for the prevention and treatment of inflammatory bowel disease (IBD), Yale University researchers have identified a previously unknown sensor regulating the composition of certain ...

Neurons play role in controlling innate immunity in presence of pathogens

April 13, 2011
There is finally definitive proof in a preclinical study published in Science on April 7 about which sensory neurons control innate (inborn and immediate) immunity in a pathogen’s presence.

Recommended for you

Australian researchers in peanut allergy breakthrough

August 17, 2017
Australian researchers have reported a major breakthrough in the relief of deadly peanut allergy with the discovery of a long-lasting treatment they say offers hope that a cure will soon be possible.

Genetic variants found to play key role in human immune system

August 16, 2017
It is widely recognized that people respond differently to infections. This can partially be explained by genetics, shows a new study published today in Nature Communications by an international collaboration of researchers ...

Study identifies a new way to prevent a deadly fungal infection spreading to the brain

August 16, 2017
Research led by the University of Birmingham has discovered a way to stop a deadly fungus from 'hijacking' the body's immune system and spreading to the brain.

Biophysics explains how immune cells kill bacteria

August 16, 2017
(Tokyo, August 16) A new data analysis technique, moving subtrajectory analysis, designed by researchers at Tokyo Institute of Technology, defines the dynamics and kinetics of key molecules in the immune response to an infection. ...

How a nutrient, glutamine, can control gene programs in cells

August 15, 2017
The 200 different types of cells in the body all start with the same DNA genome. To differentiate into families of bone cells, muscle cells, blood cells, neurons and the rest, differing gene programs have to be turned on ...

Scientists identify gene that controls immune response to chronic viral infections

August 15, 2017
For nearly 20 years, Tatyana Golovkina, PhD, a microbiologist, geneticist and immunologist at the University of Chicago, has been working on a particularly thorny problem: Why are some people and animals able to fend off ...

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.