Characterization of the determinants of snail-schistosome compatibility

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Schistosomiasis is a disease caused by parasitic flatworms of the genus Schistosoma. It afflicts over 260 million people worldwide, and the disability-adjusted life years lost to this disease rival that of malaria. As a part of their life cycle, schistosomes must undertake their larval development within a specific species of snail. Snails serve as the intermediate host for almost every one of the ~18,000 different species of parasite flatworm, and their importance to the success of the parasite is highlighted by the fact that the presence of a compatible snail host often defines the geographical distribution of trematode diseases like schistosomiasis. There is a great deal of interest in advancing our understanding of what makes one snail compatible with a particular parasitic flatworm species, and another incompatible. Schistosoma mansoni, which causes intestinal schistosomiasis in humans, has emerged along with one of its compatible snail host species, Biomphalaria glabrata, as a model for studying the determinants of snail-schistosome compatibility. Studies of this model have identified humoral and cellular factors associated with the B. glabrata immune response as key determinants of infection outcomes, acting in concert with host and parasite genetics/epigenetics, proteomic/transcriptomic regulation and environmental factors.Our investigations have focused on characterizing the interface of the cellular and humoral elements of the B. glabrata immune response during challenge by larval S. mansoni. Encapsulation of the parasite by snail immune cells is critical for elimination of the infection. Thus, it is essential for snails to maintain sufficient immune cell populations, to be able to recruit those cells to the parasite surface and have those cells initiate the proper immune effectors to kill the parasite. Our past work touched on each of these elements of a successful response by characterizing the first cellular growth factor in a snail and demonstrating that the cells that develop from stimulation by that growth factor are better suited for killing of S. mansoni. Now, because of this work, we have greater insight into the immune processes taking place within B. glabrata. We also have reagents and bioassays that allow us to investigate snail immune processes with a mechanistic lens. We propose to continue our work characterizing the B. glabrata immune response to S. mansoni challenge by addressing two specific objectives that we have identified as being central to successful parasite clearance by the snail and that build upon our past NSERC DG-supported work:1. To characterize the process of B. glabrata haemocyte development and to establish the role of specific haemocyte subsets during the cell-mediated anti-schistosome immune response.2. To investigate the circulating humoral immune factors produced by haemocytes facilitating cell-mediated killing of the larval parasite.