The long term goal of the proposed research is to understand the molecular basis for innate immune resistance in the snail, Biomphalaria glabrata, to infection by larval Schistosoma mansoni. In resistant (R) snails, primary sporocysts of the parasite are encapsulated and killed by hemocytes, whereas in susceptible (S) snails, hemocytes fail to encapsulate the parasite in vivo, and although capable of sporocyst adherence in vitro, fail to mount a cytotoxic response. Based on these distinctive cellular behaviors, it is hypothesized that S and R strain hemocytes possess strain-specific surface membrane receptors responsible for adhesion, motility, and cellular activation. In this research project, hemocytes of S and R strains of B. glabrata will be compared at the biochemical and molecular levels for cellular proteins that are differentially expressed or whose expression is induced by larval infection. The focus of these comparisons will include a RGD-binding, integrin-like surface receptor functioning in adhesion, uniquely-expressed hemocyte genes identified by differential display of mRNA, flow cytometric analyses of hemocyte receptors for sporocyst secretory and tegumental glycopeptides, and cell receptors involved in cell activation. Cells of the B. glabrata embryonic (Bge) cell line will be used to develop specific molecular probes to aid in identification and isolation of homologous molecules in hemocytes, and to serve as a potential genetic transformation system for expressing hemocyte genes of interest.
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