The specific aims of the proposal emphasize the population dynamics of the larval stages of Strongyloides stercoralis in both their enteral and parenteral phases and have been expanded to include limited initial studies of mast-cel-related containment of the enternal phase of the infection.
These aims i nclude: 1) Studies of interrupted tissue migration, particularly (but not exclusively) with regard to the skin and muscles, to determine the proportion of larvae that interrupt migration after percutaneous infection and autoinfection. We also plan to assess the importance of the skin, muscles and other tissues within which migration is interrupted as sites for survival of larvae in chronic infections, for larval destruction in immunologically sensitized hosts, or, in the case of other tissues, as foci for extraintestinal development in severely immunocomprised hosts. 2) Elucidation of factors controlling the rate of intraintestinal development that normally result in most larvae leaving the body as preinfective, rhabditiform larvae, by which allow a few to attain infectivity internally, or alternatively, under certain conditions (e.g. immunodepression), allow many to attain infectivity in the intestines. We approach this problem with an innovative, contrarian, development hypothesis. 3) To determine whether, as recently suggested for simian strongyloidiasis, local mastocytosis and release of mast cell mediators correlate with critical developmental events in the intestinal life of the parasite, thereby implicating these cells in the regulation and containment of the parasite. Larval population dynamics will be investigated using culture- derived, radiolabeled S. stercoralis larvae and commercially reared dogs. To obtain larvae differing in early developmental history with respect to the host's immunological status, parasites will be taken directly from hosts with differing levels of resistance and used to infect other experimentally manipulated hosts. Intestinal and other tissues will be examined biochemically, histologically, and immunologically to assess the role of mast cells in regulating the parasite's abundance and distribution.
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