Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Possible Strategy Identified to Combat Major Parasitic Tropical Disease

20.02.2015

St. Jude Children’s Research Hospital scientists report results that suggest neutralizing a single protein may aid fight against a parasitic tropical disease that annually sickens more than 1.3 million people worldwide

Research led by St. Jude Children’s Research Hospital scientists has identified a potential target in the quest to develop a more effective treatment for leishmaniasis, a parasitic tropical disease that kills thousands and sickens more than 1 million people worldwide each year. The findings were published online in the Journal of Clinical Investigation.


Peter Barta, St. Jude Children's Research Hospital

Research led by St. Jude Children’s Research Hospital scientists has identified a potential target in the quest to develop a more effective treatment for leishmaniasis, a parasitic tropical disease. Pictured are the study’s corresponding author, Thirumala-Devi Kanneganti, PhD, member in the St. Jude Immunology Department, and first author Prajwal Gurung, PhD, a postdoctoral fellow in Kanneganti’s laboratory.

Researchers showed that blocking the activity of the chemical messenger or cytokine called interleukin 18 (IL-18) protected specially bred mice from the most common form of leishmaniasis. IL-18 is produced by cells in the innate immune system, which serves as the first line of defense against infectious agents and other threats. Multi-protein complexes known as NLRP3 inflammasomes sense Leishmania and help to make IL-18.

The finding was a surprise because in previous research with a different mouse model, NLRP3 inflammasome was reported to drive the immune response that protects against leishmaniasis.

“We have uncovered a novel role for IL-18 in certain settings that has potential for being translated into more effective therapy for an infection that takes a high toll on residents, particularly children, of some of the world’s poorest countries,” said corresponding author Thirumala-Devi Kanneganti, Ph.D., a member of the St. Jude Department of Immunology.

Leishmaniasis is caused by a family of parasites transmitted through the bite of infected sandflies. The World Health Organization estimates that 1.3 million individuals worldwide, mostly in the developing world, are infected annually and 20,000 to 30,000 die. In countries where the disease is endemic, children are at greater risk of infection than adults. Prevention and treatment efforts have lagged. Leishmaniasis is classified as a neglected tropical disease by the U.S. Centers for Disease Control and Prevention.

The findings also provide insight into the immune response to parasitic infections, particularly how the innate immune response influences the adaptive immune response and thus the odds of eliminating the infection. Along with providing initial defense against an infection, the innate immune system shapes the more targeted defense mounted by the adaptive immune system.

This study focused on the Leishmania major (L. major) parasite, which is one of more than 20 different species of Leishmania and the most common cause of the disease in humans. L. major causes skin sores that sometimes take years to heal and result in scarring and disability.

In mice that are susceptible to the parasite, researchers reported that the infection led to increased production of IL-18 by white blood cells, which are part of the innate immune response.

Based on previous studies with a different mouse model of leishmaniasis, researchers expected IL-18 to promote an adaptive immune response led by a family of white blood cells called type 1 helper T (Th1) cells. Th1 cells make the cytokine interferon gamma that is associated with resistance to leishmaniasis.

But rather than prompting the adaptive immune system to launch a response likely to eliminate the infection, IL-18 did the opposite. IL-18 favored production of specialized immune cells that make the cytokine interleukin 4 (IL-4). IL-4 skewed the adaptive immune response in the parasite’s favor. IL-4 is produced by type 2 helper T cells.

IL-18 production is controlled by a large, multi-protein complex known as the NLRP3 inflammasome. When researchers eliminated any of the three main components of the NLRP3 inflammasome, IL-18 production declined and the mice were resistant to the infection.

“While the NLRP3 inflammasome is considered an essential component of the defense against bacterial and viral infections, little was known about its role during parasitic infections,” said first author Prajwal Gurung, Ph.D., a postdoctoral fellow in Kanneganti’s laboratory. “Our results suggest that the NLRP3 inflammasome controls susceptibility to the most common Leishmania infection by regulating the balance between the Th1 and Th2 adaptive immune response.”

Researchers also demonstrated that neutralizing IL-18 protected susceptible mice from infection, suggesting that the same approach might protect humans.

The study’s other authors are Rajendra Karki, Peter Vogel and Mark Bix, all of St. Jude; Makiko Watanabe of the University of Florida, Gainesville; and Mohamed Lamkanfi of Ghent University, Ghent, Belgium.

The study was funded in part by grants (AR056296, CA163507, AI101935) from the National Institutes of Health; the European Research Council, the Fund for Scientific Research-Flanders and ALSAC.

St. Jude Media Relations Contacts
Carrie Strehlau
desk (901) 595-2295
cell (901) 297-9875
carrie.strehlau@stjude.org

Summer Freeman
desk (901) 595-3061
cell (901) 297-9861
summer.freeman@stjude.org

St. Jude Children’s Research Hospital
St. Jude Children’s Research Hospital is leading the way the world understands, treats and defeats childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude is working to increase the overall survival rate for childhood cancer to 90 percent in the next decade. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food—because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude at @stjuderesearch.

Carrie Strehlau | newswise
Further information:
http://www.stjude.org

More articles from Health and Medicine:

nachricht Mutations in donors' stem cells may cause problems for cancer patients
17.01.2020 | Washington University School of Medicine

nachricht Overactive brain waves trigger essential tremor
17.01.2020 | Columbia University Irving Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Miniature double glazing: Material developed which is heat-insulating and heat-conducting at the same time

Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.

Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...

Im Focus: Fraunhofer IAF establishes an application laboratory for quantum sensors

In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.

The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...

Im Focus: How Cells Assemble Their Skeleton

Researchers study the formation of microtubules

Microtubules, filamentous structures within the cell, are required for many important processes, including cell division and intracellular transport. A...

Im Focus: World Premiere in Zurich: Machine keeps human livers alive for one week outside of the body

Researchers from the University Hospital Zurich, ETH Zurich, Wyss Zurich and the University of Zurich have developed a machine that repairs injured human livers and keep them alive outside the body for one week. This breakthrough may increase the number of available organs for transplantation saving many lives of patients with severe liver diseases or cancer.

Until now, livers could be stored safely outside the body for only a few hours. With the novel perfusion technology, livers - and even injured livers - can now...

Im Focus: SuperTIGER on its second prowl -- 130,000 feet above Antarctica

A balloon-borne scientific instrument designed to study the origin of cosmic rays is taking its second turn high above the continent of Antarctica three and a half weeks after its launch.

SuperTIGER (Super Trans-Iron Galactic Element Recorder) is designed to measure the rare, heavy elements in cosmic rays that hold clues about their origins...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

„Advanced Battery Power“- Conference, Contributions are welcome!

07.01.2020 | Event News

 
Latest News

A new 'cool' blue

17.01.2020 | Life Sciences

EU-project SONAR: Better batteries for electricity from renewable energy sources

17.01.2020 | Power and Electrical Engineering

Neuromuscular organoid: It’s contracting!

17.01.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>