The long-term objective of the proposed research is to define and characterize the molecular mechanisms underlying genetically-determined resistance and susceptibility in snails Biomphalaria glabrata to infection by larval Schistosoma mansoni, causative agent of human schistosomiasis mansoni. Defined susceptible (S) and resistant (R) strains of B. glabrata will be employed in comparative biochemical and immunological studies designed to provide an indepth analysis of the molecular interaction between snail hemocytes (primary anti-parasite effector cells) and the early intramolluscan stages of S. mansoni (miracidium, primary sporocyst). Surface polypeptides from S and R strain hemocytes will be labeled using a highly sensitive biotin-avidin system and subjected to SDS-PAGE analyses to compare the occurrence of individual surface polypeptides on cells of each host strain, and to determine which of the identified components serve as binding receptors for larval excretory-secretory proteins (ESP) or sporocyst tegumental surface proteins (TSP). S and R snail hemocyte cDNA expression libraries also will be constructed, and screened with hemocyte membrane-reactive antisera to identify cDNA inserts encoding potential cell surface polypeptides. Expressed recombinant hemocyte proteins will then be used in further structural comparisons between snail strains, and tested for their abilities to bind S. mansoni ESP/TSP and to alter hemocyte function as a consequence of binding. Finally, individual ESP and TSP components will be isolated by high performance liquid chromatography and preparative PAGE, and evaluated for their ability to bind S and R hemocyte surface proteins (receptors) and to modulate hemocyte-sporocyst interactions. this focused research plan directly addresses questions related to the biochemical basis for hemocyte recognition and/or activation by early schistosome larvae. It is anticipated that the information generated by this research will provide important insights into the basic mechanisms of pathogen recognition by the molluscan internal defense system, and eventually may be applied to novel approaches to control invertebrate vectors of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI015503-20
Application #
2003185
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1988-07-01
Project End
1997-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
20
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Dinguirard, Nathalie; Heinemann, Codie; Yoshino, Timothy P (2018) Mass Isolation and In Vitro Cultivation of Intramolluscan Stages of the Human Blood Fluke Schistosoma Mansoni. J Vis Exp :
Dinguirard, Nathalie; Cavalcanti, MarĂ­lia G S; Wu, Xiao-Jun et al. (2018) Proteomic Analysis of Biomphalaria glabrata Hemocytes During in vitro Encapsulation of Schistosoma mansoni Sporocysts. Front Immunol 9:2773
Adema, Coen M; Hillier, LaDeana W; Jones, Catherine S et al. (2017) Corrigendum: Whole genome analysis of a schistosomiasis-transmitting freshwater snail. Nat Commun 8:16153
Wright, Brandon J; Bickham-Wright, Utibe; Yoshino, Timothy P et al. (2017) H+ channels in embryonic Biomphalaria glabrata cell membranes: Putative roles in snail host-schistosome interactions. PLoS Negl Trop Dis 11:e0005467
Geyer, Kathrin K; Niazi, Umar H; Duval, David et al. (2017) The Biomphalaria glabrata DNA methylation machinery displays spatial tissue expression, is differentially active in distinct snail populations and is modulated by interactions with Schistosoma mansoni. PLoS Negl Trop Dis 11:e0005246
Wu, Xiao-Jun; Dinguirard, Nathalie; Sabat, Grzegorz et al. (2017) Proteomic analysis of Biomphalaria glabrata plasma proteins with binding affinity to those expressed by early developing larval Schistosoma mansoni. PLoS Pathog 13:e1006081
Adema, Coen M; Hillier, LaDeana W; Jones, Catherine S et al. (2017) Whole genome analysis of a schistosomiasis-transmitting freshwater snail. Nat Commun 8:15451
Coustau, C; Gourbal, B; Duval, D et al. (2015) Advances in gastropod immunity from the study of the interaction between the snail Biomphalaria glabrata and its parasites: A review of research progress over the last decade. Fish Shellfish Immunol 46:5-16
Yoshino, Timothy P; Brown, Martha; Wu, Xiao-Jun et al. (2014) Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expression. Int J Parasitol 44:551-63
Peterson, Nathan A; Anderson, Tavis K; Yoshino, Timothy P (2013) In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the fucosyltransferase multigene family. PLoS One 8:e63299

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