Schistosomiasis is a neglected tropical disease that affects over 200 million people worldwide. It is one of the most important parasitic diseases, second only to malaria. The causative agent for this disease are trematodes of the genus Schistosoma, with S. mansoni causing the majority of infections. S. mansoni has a complex life cycle involving humans and freshwater snails such as Biomphalaria glabrata. Schistosomiasis has been difficult to control because there is no vaccine available and drug treatment does not prevent reinfection. For this reason, finding methods to interfere with the development of the parasite in the intramolluscan stages is considered a valuable alternative to curtail transmission. B. glabrata snails are well studied and have provided important insights into the biological mechanisms of host-parasite interactions. These gastropods rely on cellular and humoral components to recognize and remove pathogens including schistosome parasites. In B. glabrata the phagocytic hemocytes play an important role in the defense against schistosome parasites. In addition to hemocytes, a variety of humoral components have also been found to be important in the snail's immune response including lectins and reactive oxygen species. A recent report described a member of the Thioester-containing family of proteins (TEPs) as a new component involved in immune recognition of S. mansoni glycans. TEPs have not being characterized in B. glabrata, and we hypothesize that these proteins are differentially expressed in response to S. mansoni infection, and that their expression is correlated with snail's schistosome susceptibility. Therefore, we propose to characterize the role of TEPs in the immune response of B. glabrata snails exposed to microbial challenge, and to determine if they are involved in the snail's competence to serve as intermediate hosts for S. mansoni. In addition, we propose studies using the the Bge cell line to set the basis for understanding the molecular mechanisms and signaling pathways associated with TEPs. The information that will be obtained can be applicable to other systems in which invertebrates serve as vectors for human disease such as mosquitoes and triatomine bugs. Finally, the data collected from these experiments will lay the foundation for the preparation of future research proposals that will promote the PI to further develop into a productive and independent researcher.
Results from the proposed work will define the role of thioester-containing proteins (TEPs) in the immune response of Biomphalaria glabrata snails to microbial challenge, and determine if they are involved in the snail's competence to serve as intermediary hosts in the transmission of human schistosomiasis.