Featured Research

from universities, journals, and other organizations

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

Date:
July 2, 2012
Source:
St. Jude Children's Research Hospital
Summary:
Scientists have identified a possible new approach to defeating bacterial infections by targeting an innate immune system component in a bid to invigorate the immune response.

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 neutralizing antibodies against this protein, we can block bacterial infection. This discovery offers a completely new approach to fighting infections by targeting the host immune response rather than the bacterium," said Thirumala-Devi Kanneganti, Ph.D., an associate member of the St. Jude Department of Immunology, and the study's senior and corresponding author. Monoclonal antibodies are laboratory-produced versions of natural antibodies 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 infectious agents 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 innate immune response."

"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.

The other authors are R.K. Subba Rao Malireddi, John Lukens and Peter Vogel, all of St. Jude; John Bertin, of GlaxoSmithKline; and Mohamed Lamkanfi, of Ghent University, Belgium.

The research was supported in part by grants (AR056296 and AI101935) from the National Institutes of Health and ALSAC.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Paras K. Anand, R. K. Subbarao Malireddi, John R. Lukens, Peter Vogel, John Bertin, Mohamed Lamkanfi, Thirumala-Devi Kanneganti. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature, 2012; DOI: 10.1038/nature11250

Cite This Page:

St. Jude Children's Research Hospital. "Innate immune system protein provides a new target in war against bacterial infections." ScienceDaily. ScienceDaily, 2 July 2012. <www.sciencedaily.com/releases/2012/07/120702153208.htm>.
St. Jude Children's Research Hospital. (2012, July 2). Innate immune system protein provides a new target in war against bacterial infections. ScienceDaily. Retrieved April 21, 2014 from www.sciencedaily.com/releases/2012/07/120702153208.htm
St. Jude Children's Research Hospital. "Innate immune system protein provides a new target in war against bacterial infections." ScienceDaily. www.sciencedaily.com/releases/2012/07/120702153208.htm (accessed April 21, 2014).

Share This



More Health & Medicine News

Monday, April 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


Toward an Alternative for Antibiotics to Fight Bacterial Infections?

July 4, 2012 Mice that do not produce the receptor protein NLRP6, are better protected against bacterial infections and can more easily remove bacteria from the body. Therapeutic drugs that neutralize NLRP6 could ... read more
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins