Mucins and Lectins from Toxocara canis

Professor R M Maizels

Toxocara canis is a parasitic nematode with unique biological features which make it an ideal model system to study multicellular helminth parasites. As a result many findings have emerged first from this system. One advance has been the demonstration that tissue-dwelling larval nematodes are enveloped in a mucin-rich surface coat, and that this coat protects them from immune attack. There are 4 mucin isoforms which are heavily O-glycosylated with a blood-group-like trisaccharide. Secondly, we have shown that the same stage secretes C-type lectins, carbohydrate-binding proteins homologous to membrane proteins found in the host's immune system. This may be an example of parasite mimicry, and our hypothesis is that the parasite secretes lectins in order to block tissue inflammatory responses by host cells, which is dependent on host lectin binding to infected endothelium. One of the parasite lectins has been shown to bind directly to host endothelial cells.

The project will be to explore the relationship between parasite mucins and lectins, and the host. Purified mucins and recombinant lectins will be used to test the hypotheses that either the mucin carbohydrates or the nematode lectins interact and block normal host lectin-host carbohydrate interactions required for inflammatory immune responses. The lectin which binds directly to host cells will also be used to isolate and characterise the host ligand, presumably an oligosaccharide.