: 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 larvae of the blood fluke, Schistosoma mansoni, causative agent of human hepatosplenic schistosomiasis. These snails serve as essential intermediate hosts in parasite transmission to the human host. However, in inbred strains of B. glabrata expressing the resistant (R) phenotype, early-developing schistosome larvae (primary sporocysts) are destroyed by a rapid cellular response involving the accumulation and adherence of circulating phagocytic cells (hemocytes) around sporocysts forming multilayered capsules. By contrast, hemocytes from susceptible (S) B. glabrata do not encapsulate sporocysts in vivo, and, although capable of in vitro larval adherence, fail to mount effective parasite killing responses under in vitro conditions. Based on these distinctive cellular behaviors, it is hypothesized that hemocytes from S and R strain snails possess a subset of unique (i.e., strain-specific) surface membrane receptors that are responsible for initial binding (pattern recognition) to the larval surface tegument or its secreted products (ESP), thereby providing the initiating signal for either hemocyte immune activation or inhibition of immune responsiveness. Results of research performed during the last grant period strongly implicate carbohydrate (CHO)-binding hemocyte lectin-like receptors (LRs) as primarily responsible for mediating initial binding interactions with the sporocyst tegument and secreted ESP. Therefore, the current project will focus on the isolation and molecular characterization of parasite-reactive LRs expressed on S and R strain hemocytes, determining the molecular diversity of LRs within and between S and R cells, characterizing signal transduction pathways triggered as a result of CHO-LR binding interactions, and exploring the role of naturally-occurring larval CHO, especially fucosylated oligosaccharides, as targets of host cell recognition or in modulating hemocyte function. Because of shared CHO-binding characteristics, the B. glabrata embryonic (Bge) cell line will be employed as a valuable comparative model for hemocyte LR structure and function. It is anticipated that information generated in this project will provide important insights into the mechanisms of pathogen immune recognition, which may eventually lead to more effective and novel methods for controling 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 #
5R01AI015503-29
Application #
7009288
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Costero, Adriana
Project Start
1988-07-01
Project End
2008-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
29
Fiscal Year
2006
Total Cost
$246,629
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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