Mechanisms of Pathogenesis in Giardiasis

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Project Summary Infection with Giardia intestinalis is one of the most common protozoan infections in the intestines of humans worldwide. Recent work has identified chronic and recurrent Giardia infection as a major contributor to stunting in children, and epithelial barrier disfunction is considered a key mechanism linking enteric infections with malnutrition and stunting. Defects in intestinal barrier function have been observed in humans, animal models and epithelial cell cultures infected with Giardia, but the mechanisms responsible for these defects remain poorly described. In the first aim of this proposal we will test the role of specific host signaling pathways in contributing to intestinal carrier disfunction using in vitro and animal models. In the second aim we will determine if parasite proteases are virulence determinants that trigger pathology in vitro and in vivo. Blocking these pathways could greatly reduce the pathology produced during giardiasis.