Approaches To Immunological Intervention In Schistosomia

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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 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 for schistosomiasis. Progress was achieved in the following areas during the year: 1) The activity of the IL-13 receptor was investigated in detail: studies showed that the fibrotic mechanism induced by IL-13 is directly controlled by the decoy IL-13Ra2. Mice deficient in this receptor developed much more severe liver fibrosis and died rapidly when infected with S. mansoni. The receptor also affects the viability of the parasite since fewer worms were detected in the knockout animals when chronically infected. 2) The role of innate verus T cell-derived IL-10 was investigated. The results from these studies showed that both sources of IL-10 cooperate to provide optimal protection from lethal immune-mediated pathology. Regulatory T cells were identified as the dominant producer of IL-10 in the granulomatous tissues and innate cells producing IL-10 were required for their development. 3) Mouse oligonucleotide microarrays were used to molecularly phenotype the gene expression patterns that characterize type-1 and type-2 cytokine-mediated inflammatory reactions in the lung. These studies identified several novel genes that might be involved in type-1 versus type-driven inflammation.