Analysis of the secretome of parasitic nematodes

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Infections of humans and animals with parasitic nematodes called filariae are of great clinical significance in tropical and veterinary medicine. Examples include lymphatic filariasis, caused by parasites such as Brugia malayi. Adult parasites live in the lymphatic system of humans, with their progeny, termed microfilariae, being found in the blood.  This parasite can lead to the remarkable and debilitating condition called elephantiasis, in which affected body parts, such as the legs, can swell to elephantine proportions. Canine heartworm infections, caused by Dirofilaria immitis, are a major indication for veterinary drug use in most of North America; adult worms of this species live in the large blood vessels in the cardiopulmonary circulation and can cause significant health problems in dogs.  The microfilariae are found circulating in the blood. As is true for most nematode infections, these parasites are quite specific for their hosts.  Indeed, host animals are not susceptible to infection by the vast majority of parasite species; only a few parasite species are capable of mounting a successful infection in any particular host.  How this host-parasite specificity is established is unknown for almost all parasites.  Understanding why a few parasites are able to overcome the otherwise highly effective antiparasitic defenses of hosts will identify completely new approaches to the control of these infections.  Before that goal can be realized, however, we must develop a thorough understanding of how parasites evade host defenses at a molecular level. Our aim is to characterize the entire set of proteins secreted by microfilariae (called the 'secretome') that protect them from destruction by the host immune response, which is normally so efficient at removing foreign objects from the blood.  In addition, we will study the biology of the secretory process of these parasites in order to comprehend how the parasite deploys it to establish a successful infection.