Because the duration and severity of giardiasis are extremely variable, it is important to study the effects of components of the intestinal milieu on survival and behavior of G. lamblia. Breast milk is a rich source of immune and non-immune secretory factors. In the initial grant period, non-human (but not cow, or goat) milk was shown to kill G. lamblia trophozoites in vitro. The kiling, which was antibody-independent, required a bile salt and is due to milk bile salt stimulated lipase (BSL). Human duodenal (but not colonic) mucus protected the parasites from milk and also promoted their attachment. These studies lead logically to the specific aims of the proposed continuation. 1. To determine the cellular and molecular mechanisms of non-immune killing of G. lamblia by human milk. 2. To elucidate the interactions of G. lamblia with complex elements of the human intestinal milieu; including: a) trophozoite attachment to human intestinal epithelial cells (IEC) and effects of IEC on parasite survival; b) chemotaxis of G. lamblia toward IEC or its metabolites; c) purification and characterization of the mucus component(s) which promote attachment and protect the parasites. 3. To delineate the effects of secretory antibodies (from human milk) on G. lamblia behaviors, including: attachment to IEC, chemotaxis, growth, survival, and killing by BSL. 4. To isolate and analyze G. lamblia behavioral mutants. 5. To determine a) whether attachment or chemotaxis mutants are infective for mice and b) whether NHM and/or human secretory antibodies can passively protect mice from G. lamblia. Information gained from these studies will provide increased understanding of the roles of immune and non-immune host secretory factors upon the course of human giardiasis.
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