This is a resubmission of an application previously reviewed in this study section. The principal investigator proposes to investigate the neuro-pathological and immunological aspects of tissues obtained from humans infested with the larval form of Taenia soleum. In addition she proposes to investigate an experimental cisticersosis (T crassiceps) in mice. The application has three Specific Aims. In the first Aim the principal investigator wishes to characterize the inflammatory response and the immunological reactions to T soleum larvae in the CNS of humans. She has arranged to obtain appropriately frozen larval excisions, cyst fluid and CSF samples of such patients from collaborators in Mexico (where the disease is far more prevalent). First she will determine the cell types present in the CNS material using immunohistochemistry specific for the cellular elements of the CNS. in addition Tg/d cells will be sought. Next she will define the adhesion molecules expressed on and in the region of the parasitic cysts. Chemokines and cytokine profiles will also be established. In addition to immunohistochemistry, she will use in situ hybridization and in situ PCR to localize these cytokines/chemokines in the inflammatory infiltrate. Special attention will be directed to cytokines believed responsible for immuno-suppression of the reaction. Finally, she will seek evidence of apoptosis or immune activation of the cells (native and infiltrating) in the vicinity of the larval cysts. The second Specific Aim is to attempt to correlate the findings of the first Specific Aim with the corresponding levels of cytokines in the CSF or peripheral blood.
Her final Aim i s to utilize a murine system of CNS larval infestation by T crassiceps and/or M corti to validate and render coherent her findings in the human tissues. This system will be much more controlled and manipulable. In addition, the scope of reagents available for these studies in a murine system should permit a more detailed dissection of the murine Teania system. Under this Aim she will first define the pathology, the inflammatory infiltrates, the cytokine production and adhesion molecule expression in infested mouse liver and brain tissue. (It is noted that T crassiceps does not infest brain, but M corti can be made to do so following intracerebral injection. In this system she can examine the effect on the immune response of the living parasite, and following administration of anti-helmenthic agents, observe the response to degenerating parasitic cysts. In a second part of this Aim, she will screen a variety of murine strains for variations in susceptibility to infestation by these organisms. Special attention will be directed toward mice deficient in IgE production which is believed important in defining the host-parasite relationship. Finally, she will utilize a variety of gene knock-out mice (IL4, IL10, TGFb, E-selectin, CD40 and IFNg knock outs will be available for study).
Showing the most recent 10 out of 41 publications
