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.
| Letonja, T; Hammerberg, C; Davis, S et al. (1988) Taenia taeniaeformis: cellular reconstruction of athymic mice and role of L3T4+ helper T lymphocytes in the early infection. J Parasitol 74:985-92 |
| Letonja, T; Hammerberg, C (1987) Taenia taeniaeformis: early inflammatory response around developing metacestodes in the liver of resistant and susceptible mice II. Histochemistry and cytochemistry. J Parasitol 73:971-9 |
