Principle Investigator/Program Director: Yoshino, TEimothy P. 0 take an integrated cellular, biochemical and molecular approach to evaluate the role of hemocyte pattern The primary objective of the current research program is to define and characterize the molecular basis for schistosome-specific CHOs. The central hypothesis to be addressed is that parasite CHOs represent the recognition receptors, emphasizing CHO-reactive lectins, in immune recognition of and reactivity to expressed carbohydrates (CHO5) and hemocyte immune function. As a result, the current research plan will Information gained over the last grant period strengthens a critical, but complex, nexus between larval- of the human blood fluke Schistosoma mansaril, causative agent of hepatosplenic schistosomiasis. innate resistance and susceptibility of inbred strains of the snail Biomphalaria glabrat.;9a to infection by larvae 3N. ?-L) together initial hemocyte-CHO interaction and expression of hemocyte effector function (ROS response). In to early developing schistosomes, this work will contribute to a greater understanding of the mechanisms of primary pathogen-associated molecular patterns (PAMPs) responsible for hemocyte immune recognition, but innate immune recognition and pathogen anti-immune responses that may well lead to the development of addition to providing important insights into the role of schistosome CHOs in regulating hemocyte responses anticipated that research findings generated as a result of this project will provide a unifying model linking antioxidant responses as possible factors in regulating cytotoxic reactivities of S and R snail hemocytes. It is responses or generation of reactive oxygen species (ROS), and (3) explore the role of endogenous parasite lectin-like receptors, and if so, whether they are capable of eliciting or inhibiting hemocyte encapsulation known hemocyte lectin-like receptors, (2) determining if schistosome-specific CHOs serve as ligands for hypothesis, research efforts will be directed towards (1) characterizing structural and functional properties of required for effector activity, or relative sensitivities to """"""""anti-immune"""""""" parasite mechanisms. To address this oxidative responses) are due either to differences in CHO-recognizing receptors, receptor repertoires, signals differential responses by susceptible (5) and resistant (R) snail cells (e.g., CHO-reactivity, larval adherence, 0 2'U R,< yin 9'm .p-. a); OTC M,.' mm0 non u.ma ,p.,. a""""""""' .0.. Q-- o.- C7K 3 novel approaches to controlling these snail vectors of human disease or the pathogens they carry. .L..

Public Health Relevance

The primary goal of the current project is to define and characterize the molecular basis for innate immune resistance of inbred strains of the snail Biomphalaria glabrata to infection by larvae of the human blood fluke Schistosoma mansoni, causative agent of hepatosplenic schistosomiasis. Schistosome parasites infect an estimated 200 million people in over 70 countries worldwide, severely impacting the general public health, vitality, and productivity of affected populations, especially developing nations in the tropics. Because these pathogens require snail intermediate hosts for completing their life cycle and transmission to humans, information on the mechanisms of immune reactivity in snails against larval infection will be critical in understanding the genetic basis for host resistance. Therefore, knowledge gained from the proposed studies could very well lead to the development of more effective and novel methods for controlling human schistosome transmission by disrupting parasite development within the snail host.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI015503-31A1
Application #
7822397
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
1988-07-01
Project End
2010-05-31
Budget Start
2009-06-19
Budget End
2010-05-31
Support Year
31
Fiscal Year
2009
Total Cost
$293,120
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; Cavalcanti, Marília 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
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
Soares, Cláudia Sossai; Morais, Enyara Rezende; Magalhães, Lizandra G et al. (2013) Molecular and functional characterization of a putative PA28? proteasome activator orthologue in Schistosoma mansoni. Mol Biochem Parasitol 189:14-25
Peterson, Nathan A; Anderson, Tavis K; Wu, Xiao-Jun et al. (2013) In silico analysis of the fucosylation-associated genome of the human blood fluke Schistosoma mansoni: cloning and characterization of the enzymes involved in GDP-L-fucose synthesis and Golgi import. Parasit Vectors 6:201
Yoshino, T P; Bickham, U; Bayne, C J (2013) Molluscan cells in culture: primary cell cultures and cell lines. Can J Zool 91:
Yoshino, Timothy P; Dinguirard, Nathalie; Mourão, Marina de Moraes (2010) In vitro manipulation of gene expression in larval Schistosoma: a model for postgenomic approaches in Trematoda. Parasitology 137:463-83
Wu, Xiao-Jun; Sabat, Greg; Brown, James F et al. (2009) Proteomic analysis of Schistosoma mansoni proteins released during in vitro miracidium-to-sporocyst transformation. Mol Biochem Parasitol 164:32-44
Peterson, Nathan A; Hokke, Cornelis H; Deelder, André M et al. (2009) Glycotope analysis in miracidia and primary sporocysts of Schistosoma mansoni: differential expression during the miracidium-to-sporocyst transformation. Int J Parasitol 39:1331-44