The long-term objectives of this project are to identify mechanisms of resistance and susceptibility operating during early cysticercosis and to define the genetic basis for these mechanisms. Larval Taenia taeniaeformis infections in rodents provide a well studied model for severely debilitating human metacestode infections such as those from Taenia solium (pork derived cysticercosis) and Echinococcus granulosis or E multilocularis (hydatid or alveolar disease), and the greatest analogy among these infections occurs during the earliest stages of infection. Therefore, the specific aims of this project are: 1) to quantitate the attachment and penetration of invading oncosphere in the duodenum of resistant and susceptible mice by intestinal lavage with activated oncospheres, 2) to describe the leukocyte response, including determination of the lymphocyte population, occurring around activated oncospheres and developing larvae in the livers of resistant and susceptible mice, 3) to characterize the functional changes occurring in spleen cells during the first 6 days of infection by quantitating delayed type hypersensitivity and production of lymphokines, 4) to characterize the interactions of oncospheres and early stages larvae with host complement cascade proteins and 5) to establish, through the use of recombinant inbred and congenic strains, the precise genetic control of those immune or inflammatory responses which have been found in 1), 3) and 4) above to bb distinctly different in resistant and susceptible mice. The early leukocyte response will be determined 1- to 6- days post-infection by: 1) immuno-histological analysis with monoclonal antibodies (MAb) against cell surface antigens (Lyt-1, Lyt-2, Thy-1 and Mac-1) of leukocytes adjacent to oncospheres in liver tissue, 2) delayed foot pad reaction and lymphokine production against a Taenia oncosphere antigen, 3) determining the cellular subset involved in the response to Taenia by cellular depletion of splenic lymphocytes with MAb against Lyt-1, Lyt-2 and Thy-1 plus complement and testing for their in vivo and in vitro responses to T. taeniaeformis and 4) examining the response of PMN cells to the larvae in vitro. The interaction between complement and the larvae will be measured at three levels: 1) antibody independent lysis of early stage parasites, 3) complement component C3 deposition on oncospheres and developing larvae and 3) complement protein C5 activation by in vitro culturing of mouse sera with oncospheres and determining C5a chemotactic activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI020914-03
Application #
3130727
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Virginia Polytechnic Institute and State University
Department
Type
Schools of Veterinary Medicine
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24060