A chemical released by intestinal worms to prevent the immune system attacking them has been isolated by scientists in Glasgow. It might, they say, provide us with a new way to control inflammatory reactions and prevent organ rejection in future.
Parasites, like the intenstinal worms that live inside our bodies, have to ensure that they stay below the immune radar to avoid being recognised and eliminated. Scientists have long suspected that this is probably achieved, at least in part, by the parasite releasing chemicals that can damp down immune responses, or throw the immune system off the scent.
The evidence for this theory is that in parts of the world where parasitic infections are more common, such as rural Africa, the rates of allergy and autoimmune diseases like arthritis are much less common. Studies have also been carried out in both animals and on human volunteers showing that being colonised by intestinal worms can reduce the severity of conditions like ulcerative colitis, where the immune system damages the lining of the large bowel. How the parasites achieve this though, scientists were not sure.
Now researchers at the University of Glasgow have isolated a previously undiscovered factor, which is released by a worm that lives in the intestines of mice and has a powerful moderating influence on the host's immune system.
The worm in question is called Heligmosomoides polygyrus. Most mice carry about 12 of these coiled roundworms in their intestines at any one time. The worms shed eggs into their host's faeces. These hatch in the environment and the microscopic larvae are picked up by other mice when they forage.
To prevent the immune system from mounting a defence against it, the parasite releases various chemicals into the intestine. The Glasgow group collected and purified this cocktail, and added the different components to cells in a culture dish.
One of the components they tested powerfully mimicked the action of an immune signal called TGF-beta. This has a number of roles in the body, one of which is to stimulate the production of a population of cells known as regulatory T cells, or TREGs, which can damp down immune responses.
In the culture dish, this new worm factor, dubbed by the team Hp-TGM (short for H. polygyrus TGF-beta mimic), powerfully induced both mouse and human immune cells to turn into large numbers of TREGs. In fact, the effect was more pronounced than the body's own native TGF-beta signal.
Hp-TGM was also effective in vivo. Mice given injections of the agent following an incompatible skin graft took nearly 50% longer to reject the graft compared to control animals.
According to lead author Chris Johnston and his colleagues, who have published the work in the latest edition of Nature Communications, the discovery may offer a new way to manipulate the immune system but with fewer of the side effects associated with traditional immune-suppressing therapies since the effects of Hp-TGM appear to be so discrete and specific.
Injecting the agent may also not even be necessary, the team point out, since it could be used to manipulate a patient's immune cells outside the body to boost the number of TREGs. Once these had been checked for safety, they could be re-infused into the patient to exert their immune-stabilising effects...
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