Research Report 2016 - Asthma, Allergy and Parasitic Diseases
Parasitic worms have evolved complex mechanisms to subdue the immune system of their host, to enable them to survive and reproduce. The mechanisms they use to dampen harmful inflammatory immune responses are studied to find new treatments for asthma and allergic diseases.
The Asthma, Allergy and Parasitic Diseases group uses studies of allergens and parasites (Heligmosomoides polygyrus, a gut worm and Nippostrongylus brasiliensis), to understand the basic mechanisms that cause asthma and allergic diseases. As a spin-off, the group is also developing insight in how to make effective vaccines against parasites.
Mali Camberis, Research Manager of the Allergic and Parasitic Diseases Programme says understanding the basic mechanisms used by the host to kill parasitic larvae underpins all their allergy research.
“We’re working on constructing the genome for N. brasiliensis, so we can look at the activation of different genes during the lifecycle of the worms – through their four larval to the adult stage. We see a large number of changes when the larvae enter the host and start feeding on blood, through the L3 to L4 stage. By understanding which genes are activated and deactivated, we may be able to design potential new drug targets to target this phase and prevent the harmful parasites entering the lung, where they cause damage,” she says.
The Sabin Vaccine Institute and the Center for Vaccine Awareness and Research at Texas Children’s Hospital in the United States have invited the Malaghan Institute to test new human hookworm vaccine candidates in the Institute’s mouse model. The vaccine development work is funded by the Bill and Melinda Gates Foundation.
Hookworm is a huge problem in the developing world, so we are pleased to be able to contribute to research that is close to clinical trial stage. It’s also beneficial for us as it will validate our in-house assay as a model of human hookworm.
Another project is studying the effect of infection with more than one parasite on the immune system, modelling real life scenarios for many people in the developing world. Early results have shown that infection with the gut parasite, H. polygyrus causes protection (even in the lung) from infection with the second parasite N. brasiliensis. Research to unravel the mechanisms behind this observation is continuing.
Infection with H. polygyrus has also been shown to suppress several autoimmune diseases, such as allergic airway inflammation and colitis. Several models of skin allergy are being used to see if there are improvements to these conditions when the parasite is present. A cross-over allergy research project is investigating the cellular and molecular events that occur in the first 24–48 hours after infection with N. brasiliensis. “We are using the parasite to sensitise the skin as the first step in an allergic reaction and observing the changes with our confocal microscope. This work will add to our understanding of how the parasites interact with the immune system and could also help identify new molecular therapeutic targets.”
Professor Graham Le Gros, Mali Camberis, Jodie Chandler, Dr David Eccles, Dr Kara Filbey