In many of the developing countries of the world, schistosomiasis, fascioliasis, and other snail-borne parasites continue to impose an intolerable burden of human suffering, and of diminished productivity of domestic animals. The long term goal of the proposed research is to better understand the complex and evolutionarily ancient associations between larval flukes and their snail hosts. By learning how larval trematodes evade or suppress the internal defense systems of their molluscan hosts, the changes of successfully mitigating the impact of such parasites through implementation of rational control measures are increased. The available evidence suggests that larvae of some, and perhaps all, trematode species actively suppress the snail's immune system, a phenomenon termed interference (Lie 1982). Recent work implies that hemocytes, the circulating immune cells of snails, are the targets of interference, and indirect evidence suggests that the effect can be mediated by soluble factors released from trematode larvae. Using the trematode Echinostoma paraennsei and the snail Biomphalaria glabrata as a model system, the proposed research seeks to define more precisely the effects of infection on hemocytes, and to provide more direct evidence for the role of trematode secretory/excretory products (SEP) in mediating interference. E. paraensei has several advantageous properties for such a study: its suppressive effects are known to be strong, its larvae can be easily collected in large numbers, and its in vivo development can be unobtrusively studied. Lectins and anti-hemocyte or anti-SEP antibodies will be used as probes to assess alterations in hemocyte surfaces resulting from infection. Also, E. paraensei larvae will be cultured in vitro, and their SEP will be collected, and characterized using SDS-PAGE electrophoresis. SEP will be injected into snails to learn if SEP can mimic the effects of infection, or alter the snail's resistance to infection with E. paraensei or Schistosoma mansoni. Anti-SEP will be used in conjunction with immunoblotting to determine if SEP binds to hemocytes. The proteolytic and anti-proteolytic effects of SEP will be assessed. This research will more precisely define the manner in which trematode suppression is mediated, and will set the stage for isolation and characterization of specific components of SEP with biological relevance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI024340-01
Application #
3137318
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1986-12-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of New Mexico
Department
Type
Schools of Arts and Sciences
DUNS #
829868723
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Hanington, Patrick C; Forys, Michelle A; Loker, Eric S (2012) A somatically diversified defense factor, FREP3, is a determinant of snail resistance to schistosome infection. PLoS Negl Trop Dis 6:e1591
Loker, Eric S (2012) Macroevolutionary Immunology: A Role for Immunity in the Diversification of Animal life. Front Immunol 3:25
Hanington, Patrick C; Zhang, Si-Ming (2011) The primary role of fibrinogen-related proteins in invertebrates is defense, not coagulation. J Innate Immun 3:17-27
Adema, Coen M; Hanington, Patrick C; Lun, Cheng-Man et al. (2010) Differential transcriptomic responses of Biomphalaria glabrata (Gastropoda, Mollusca) to bacteria and metazoan parasites, Schistosoma mansoni and Echinostoma paraensei (Digenea, Platyhelminthes). Mol Immunol 47:849-60
Loker, Eric S (2010) Gastropod immunobiology. Adv Exp Med Biol 708:17-43
Hanington, Patrick C; Lun, Cheng-Man; Adema, Coen M et al. (2010) Time series analysis of the transcriptional responses of Biomphalaria glabrata throughout the course of intramolluscan development of Schistosoma mansoni and Echinostoma paraensei. Int J Parasitol 40:819-31
Hanington, Patrick C; Forys, Michelle A; Dragoo, Jerry W et al. (2010) Role for a somatically diversified lectin in resistance of an invertebrate to parasite infection. Proc Natl Acad Sci U S A 107:21087-92
Hathaway, Jennifer J M; Adema, Coen M; Stout, Barbara A et al. (2010) Identification of protein components of egg masses indicates parental investment in immunoprotection of offspring by Biomphalaria glabrata (gastropoda, mollusca). Dev Comp Immunol 34:425-35
Zhang, Si-Ming; Nian, Hong; Wang, Bo et al. (2009) Schistosomin from the snail Biomphalaria glabrata: expression studies suggest no involvement in trematode-mediated castration. Mol Biochem Parasitol 165:79-86
Adema, Coen M; Luo, Mei-Zhong; Hanelt, Ben et al. (2006) A bacterial artificial chromosome library for Biomphalaria glabrata, intermediate snail host of Schistosoma mansoni. Mem Inst Oswaldo Cruz 101 Suppl 1:167-77

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