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 Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>