Navigation Links
Innate immune system protein provides a new target in war against bacterial infections
Date:7/2/2012

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 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.


'/>"/>

Contact: Summer Freeman
summer.freeman@stjude.org
901-595-3061
St. Jude Children's Research Hospital
Source:Eurekalert

Related biology news :

1. La Jolla Institute scientist discovers key step in immune system-fueled inflammation
2. Preventing the immune system from going haywire during sepsis
3. Programmable DNA scissors found for bacterial immune system
4. UGA study reveals flu-fighting role for well-known immune component
5. London researchers discover novel mechanism involved in key immune response
6. Mystery to the origin of long-lived, skin-deep immune cells uncovered
7. Breast-fed babies gut microbes contribute to healthy immune systems
8. New screening technique yields elusive compounds to block immune-regulating enzyme
9. Immune-response genes affecting breast tumor eradication
10. Carnegie Mellon fluorescent biosensor reveals mechanism critical to immune system amplification
11. New genetic mechanism of immune deficiency discovered
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/29/2017)... the health IT company that operates the largest health ... today announced a Series B investment from BlueCross BlueShield ... investment and acquisition accelerates higi,s strategy to create the ... activities through the collection and workflow integration of ambient ... secures data today on behalf of over 36 million ...
(Date:3/24/2017)... The Controller General of Immigration from Maldives Mr. Mohamed Anwar ... the prestigious international IAIR Award for the most innovative high security ePassport ... ... Maldives Immigration Controller General, Mr. ... on the right) have received the IAIR award for the "Most innovative ...
(Date:3/23/2017)... 2017 Research and Markets has announced the ... Trends - Industry Forecast to 2025" report to their offering. ... The Global ... of around 8.8% over the next decade to reach approximately $14.21 ... market estimates and forecasts for all the given segments on global ...
Breaking Biology News(10 mins):
(Date:4/25/2017)... ... April 25, 2017 , ... Covalent Metrology has ... Services unit provides high-quality data to clients, both faster and cheaper than ... There are no price premiums, and customers are welcome to participate in the ...
(Date:4/21/2017)... ... April 21, 2017 , ... ... manufactures in 10 categories with over 30 nominees and well as the first-year ... the new award and the event was hosted by CompanyWeek and Manufacturers Edge, ...
(Date:4/21/2017)... ... April 21, 2017 , ... The AMA is happy ... school graduates from across the nation. The scholarships are created through funds donated by ... , Scholarship criteria are set by the AMA Scholarship Committee, which is made up ...
(Date:4/20/2017)... (PRWEB) , ... April 20, 2017 , ... ... today announced their strategic partnership to offer a full spectrum of digital ... a comprehensive suite of biometric products and the ground-breaking proactive cybersecurity services and ...
Breaking Biology Technology: