Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers get to heart of tropical disease

23.06.2006
A new study found that mice lacking a gene crucial to the normal functioning of their immune systems didn't become ill when they were exposed to a pathogen that causes a horrendous infection in the liver and the spleen.

The pathogen, called Leishmania donovani, infects certain internal organs. The parasite causes visceral leishmaniasis which, if left untreated, is almost always fatal. Cases in the United States are extremely rare, but the disease, which is transmitted through the bite of a sand fly, is common in tropical and subtropical countries such as Iraq, Iran and Afghanistan.


Leishmania donovani in a bone marrow cell. Image credit: [CDC/Dr. L.L. Moore, Jr (PHIL #468), 1969. via Wikipedia.]

The finding may lend insight into creating new drugs to treat different diseases that affect the liver, said Abhay Satoskar, the study's lead author and an assistant professor of microbiology at Ohio State University.

The gene makes a protein called STAT1, and its production is triggered whenever the immune system senses a foreign bacterium, virus or other pathogen. STAT1 activation is a critical step in the immune system response, as this protein activates other key immune substances.

So it didn't make sense to the researchers that mice that couldn't produce STAT1 would remain healthy.

“It took us completely by surprise,” Satoskar said. “We knew from previous work that mice that lack the substances produced in response to STAT1 develop serious infections. We thought we'd see that in this study, too.”

The study appears as a Cutting Edge paper in the July 1 issue of the Journal of Immunology website.

The researchers infected groups of mice with L. donovani. Mice in one group lacked the gene that makes STAT1. Mice in another group lacked the gene that makes an immune system protein called T-bet. In a normal immune response to infection, STAT1 triggers the production of T-bet. Together, these proteins are responsible for the production of interferon gamma, an important protein that helps launch a full-blown immune system attack against foreign pathogens.

A group of mice with both STAT1 and T-bet genes intact served as a control.

About two weeks after infection, the researchers began measuring the number of L. donovani parasites in the animals' livers.

The pathogen went wild in the mice that lacked T-bet – the researchers found thousands upon thousands of the parasites in the livers of these animals.

Yet there were next to no parasites in the mice without STAT1.

“Two weeks after infection, the mice without STAT1 had 25-fold fewer parasites in their liver tissue than the normal mice, and about 100-fold fewer parasites than the mice without T-bet,” Satoskar said. “Visceral leishmaniasis never developed in the animals without STAT1 – the parasites weren't able to establish an infection in the animals' livers and spleens.”

The researchers also measured parasite levels in the livers two months after infection. Again, levels were quite high in the mice without T-bet, while normal mice and mice without STAT1 showed no sign of the disease.

While the normal mice weren't sick – they showed no physical signs of having leishmaniasis, such as inflammation of the liver and spleen – Satoskar said the parasite was still in their systems.

“Once infected, the parasite never goes away completely,” Satoskar said. “It's always hiding somewhere.”

Ironically, L. donovani thrives in the liver and spleen by infecting the very cells that the immune system uses to rid the parasite from the body. These cells are called macrophages – a kind of garbage collector for the immune system, as they clean out everything from red blood cells that have died to infectious pathogens. But enough L. donovani parasites can overtake a macrophage's ability to clean up.

“L. donovani infection failed to launch in mice without STAT1 because there weren't enough macrophages in the liver for the parasite to infect, and these are the very immune cells that are essential for successful survival and replication of Leishmania parasites in the host,” Satoskar said.

The researchers aren't suggesting that STAT1 activation should be stopped in order to prevent visceral leishmaniasis. However, they want to figure out how this protein's absence keeps macrophages from flooding into the liver during the early stages of infection.

If they can do that, it may be possible to create a drug to prevent L. donovani from infecting the liver and the spleen. Although there are medications available to treat the symptoms of visceral leishmaniasis, they can be toxic and sometimes expensive for the people who need them the most.

Satoskar conducted the study with colleagues from Ohio State, Montreal General Hospital in Montreal, Canada, and with the Harvard School of Public Health and Harvard Medical School.

This work was supported by grants from the National Institutes of Health, the National Institute of Dental and Cranial Research, the National Science Foundation and the Ellison Medical Foundation.

Abhay Satoskar | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Lightning, with a chance of antimatter

24.11.2017 | Earth Sciences

A huge hydrogen generator at the Earth's core-mantle boundary

24.11.2017 | Earth Sciences

Scientists find why CP El Niño is harder to predict than EP El Niño

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>