We study the mechanisms that parasitic worms use to subdue the immune system because of their potential to dampen harmful inflammatory immune responses, such as those made in asthma and allergy.
Over millions of years, parasitic worms have evolved complex mechanisms that enable them to survive and reproduce inside a host species by hiding from or manipulating their host’s immune system.
Human hookworm and allergy
The mechanisms by which these organisms subdue the immune system have been studied at the Malaghan Institute for many years because of their potential to dampen harmful inflammatory immune responses, such as those made in asthma and allergy.
Hookworm affects one billion people worldwide. It is a leading cause of death in developing countries. Infection is currently controlled through frequent use of drugs in school-age children, however, high rates of re-infection occur soon after treatment and there is evidence of emerging drug resistance.
We believe creating a vaccine for hookworm is a lasting way to prevent re-infection and break the cycle of disease.
We are also interested in the parasite's interaction with the immune system, because once communities are able to control the parasite, the incidence of allergies to harmless environmental allergens gradually rises.
Our research in parasitic diseases is led by Professor Graham Le Gros.
The rodent gut worm Heligmosomoides polygyrus is known to have a strong effect on its host’s immune system, inducing the production of chemicals and regulatory cells that dampen down responses towards it. Nippostrongylus brasiliensis, another rodent worm, is used in laboratory studies to model infection with human hookworm. It migrates through the skin to the bloodstream and lungs and then enters the gut, causing anaemia and tissue damage.
In other research, N. brasiliensis was given to mice already infected with H. polygyrus. (Infection with more than one worm models real world scenarios where people in Asia and Africa live with a number of parasitic worms in their bodies.) Because of the immune dampening effect of H.polygyrus, it was expected that N. brasiliensis would flourish in the mice.
Surprisingly, the exact opposite occurred and one of the most robust and repeatable protective immune responses against this worm to date was observed. Within 24 hours, N. brasiliensis parasites in the lung (a crucial and very damaging part of its life cycle) were being attacked and killed by the immune system to a much greater extent than in the mice without H.polygyrus infection.
Work to solve this mysterious result is now underway, with researchers exploring how a worm restricted to the gut (H. polygyrus) could affect immunity in distant organs like the lung. One focus is the damaging effect that H. polygyrus has on a mouse gut. During larval development, the parasites burrow into the gut lining and puncture it, allowing metabolic products and gut bacteria to leak into the bloodstream. Protein-containing secretions from the worm that modify the immune system could also be involved.
We have a strong research programmes that exames the basic biology of parasitic and non-parasitic worms. This knowledge is crucial for the development of novel forms of immunotherapy to treat allergic diseases.