Approaches/Immunological Intervention In Schistosomiasis

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Abstract

The purpose of our research program is to elucidate the molecular and immunologic mechanisms regulating the pathogenesis of schistosomiasis and other parasitic diseases. Transgenic and knockout mice are employed in these experimental studies so that basic pathogenic processes can be investigated. Key findings from our murine studies are then extended to the field, where the immune responses of schistosomiasis patients exhibiting different clinical forms of the disease are examined. The ultimate goal of this research is to understand the host immune response to infection so that immunologically based strategies might be employed in the development of a highly effective vaccine or treatment for schistosomiasis. A focus of our research is to understand the basic mechanisms of tissue remodeling and fibrosis, which are debilitating and life-threatening sequelae of a number of chronic inflammatory diseases. Strikingly, almost 45% of the deaths in the U.S.A. are believed to result from chronic fibroproliferative diseases. Progress was achieved in the following areas during the year: 1) Using diseased liver tissue and DNA microarrays, we used a novel High-Throughput integrative Gene Ontology tool called 'GoMiner' to interpret multiple-microarray experiments simulatenously. These studies identified several molecular pathways that are activated in the liver during ongoing chronic S. mansoni infection. 2) We showed that IL-13 can activate a mechanism of tissue fibrosis that is completely TGF-beta independent; and 3) The role of IL-5 and eosinophils in progressive liver fibrosis was examined. These studies revealed several novel eosinophil-associated genes, that were subsequently studied in detail.