Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Could the ability to expel worms lead to a future asthma treatment?

18.12.2006
New understanding of immune system creates unexpected links in medicine

Based on experiments with worms similar to those that infest millions of children in the tropics, researchers see potential for a new way to treat asthma. Parasitic infections and asthma may cause the human immune system to react in some of the same ways, and may one day be cured by manipulating some of the same proteins, according to research published today in the journal Science.

To be effective, the immune system must "decide" which cells and chemicals need to be ramped up to best destroy the invader at hand, be it bacterium, virus or worm. In 1986, Tim Mosmann, Ph.D., now director of the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, led a team that first described a new concept for how the immune system might make such choices: the Th1/Th2 Model. A landmark in immunology, it was a major step toward unraveling the system’s complexities. Today’s study results show how the model continues to define new players in the immune system and to suggest new treatment approaches.

"The point of the study is that each new detail in our understanding of the immune system creates opportunities to make changes that counter disease," said Mosmann. "These results, while early, suggest that helping the body make more of a newly defined immune chemical may prevent roundworm infection, and that shutting it down may reduce lung damage in asthma."

Part of the immune system is adaptive, pumping out vast numbers of immune cells on the hope that one will be the right shape to link up with, and become activated by, any invader encountered. When one of those immune cells recognizes an invader, it expands into an army of clones specifically selected to attack that organism. One workhorse of the adaptive system is the helper T cell, a white blood cell that secretes protein messengers called cytokines to accelerate the immune response.

According to Mosmann’s model, T cells differentiate into two major sets of helper T cells, Type 1 (Th1) and Type 2 (Th2), each defined by the cytokines they produce. Each profile is more effective at attacking certain invaders, with Th1 responses, for example, better against bacteria that live inside cells. Th2 cytokines include interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13), all of which are useful in immune responses against worms. In a clue to the worm/asthma link, IL-4, IL-5 and IL-13 also trigger mechanisms that cause irreversible damage to the lungs of asthmatic patients.

Study Details

How the mouse immune system reacts to the worms is central to Mosmann’s research because mice and humans share the Th1/Th2 immune system divide, because mouse and human roundworm parasites are relatives, and because roundworm infection remains a major threat in the developing world. His basic research on T cell subsets was funded by the National Institute of Allergy and Infectious Diseases.

More than 15,000 species of parasitic roundworms infect everything from grapes to wasps to cattle. In humans, infection is usually caused by eating undercooked pork or wild game, or by poor hygiene, and brings repeated episodes of diarrhea, anemia and malnutrition. Stranded soldiers were once advised by field manuals to eat a cigarette or drink a tablespoon of kerosene to stun the worms, but modern antihelminthic drugs (e.g. Albendazole, Ivermectin, Thiabendazole) are effective and much safer. Drug treatments, however, do not reach many living in the worst conditions nor do they prevent patients from becoming re-infected. Mosmann’s work could conceivably lead to a vaccine that would confer permanent immunity to worm infection, but such research remains in the future.

Having been exposed to bacteria and parasites since early in evolution, tissues lining the gut and lungs of mice and humans have developed ways to prevent invaders from entering the body. Tissues lining the gut, for example, shed their outer cell layers when exposed to worms. Helper T cells release chemicals that cause gut cells to rapidly divide and reproduce (grow). As new cells are created, older, outer, infested layers die, fall off (shed) and are expelled from the body with solid waste.

Using molecular biology techniques, Mosmann’s team found that roundworm infection led Th2 helper T cells, more than other T cell types, to produce greater amounts of a growth factor, amphiregulin, which triggers cells to divide and grow. The current results define amphiregulin for the first time as an important new player in the immune system, in the Th2 immune profile and perhaps in the many disease processes touched by it.

In the current study, mice were infected with the nematode parasite, Trichuris muris, a relative of the worm that causes trichinosis in humans. After 14 days of infection, the study found increased expression of amphiregulin along with higher levels of Th2 cytokines IL-4 and IL-13.

Researchers confirmed the relevance of amphiregulin in immune responses to the parasites by comparing worm counts in normal mice against mice that had been genetically engineered not to produce amphiregulin. Similar numbers of worm larvae were detected after ten days in both groups, and all mice cleared the parasite by day 19. Worm clearance at day 14, however, was significantly delayed in amphiregulin-deficient mice, as was the shed rate in their gut cells.

More immediate than the potential for an anti-worm vaccine, authors said, is the study’s finding for the first time that amphiregulin is a product of Th2 cells, which are known to play key roles in asthma, the chronic disorder that blocks and damages air passages in the lungs of 20 million Americans.

Researchers believe airborne irritants cause Th2 cells to release interleukins, which in turn leads to the release of toxic granules that cause direct tissue damage in the lungs. As the lung tries to heal the damage, growth factors cause the airway walls to thicken, by as much as 300 percent in severe cases. Could amphiregulin be the growth factor that causes permanent thickening of asthmatic airways, restricting airflow more and more as time goes by"

Mosmann’s team has already begun experiments to determine if the production of amphiregulin by the Th2 response in mice also occurs in human helper T cells. After that, researchers are interested in comparing amphiregulin expression levels in the cells of healthy versus asthmatic lungs.

Greg Williams | EurekAlert!
Further information:
http://www.urmc.rochester.edu

Further reports about: Asthma Mosmann’s T cells Th2 amphiregulin cytokines immune immune system parasite

More articles from Life Sciences:

nachricht O2 stable hydrogenases for applications
23.07.2018 | Max-Planck-Institut für Chemische Energiekonversion

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

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....

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

Detecting damage in non-magnetic steel with the help of magnetism

23.07.2018 | Materials Sciences

Researchers move closer to completely optical artificial neural network

23.07.2018 | Information Technology

Enabling technology in cell-based therapies: Scale-up, scale-out or program in-place

23.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>