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 Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

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: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

Nano-kirigami: 'Paper-cut' provides model for 3D intelligent nanofabrication

16.07.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>