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10 ACTIVATION OF DENDRITIC CELLS BY ENTAMOEBA HISTOLYTICA GAL-LECTIN DRIVES TH1 RESPONSES C Ivory, K Chadee Amebiasis is a human disease caused by the protozoan intestinal parasite E histolytica. The disease is prevalent in tropical countries and is a serious threat to human health. Vaccine development has focused on the parasite's surface Gal-lectin as a protective antigen. The Gal-lectin is involved in parasite colonization via its carbohydrate recognition domain for binding to colonic mucins. The Gal-lectin is immunogenic and has been shown to induce Th1 cytokines in vitro and in vivo. The immunological basis of the protective immune response elicited by the Gal-lectin is unknown. Since dendritic cells (DCs) are abundant at mucosal surfaces and would be the first immune cells to encounter enteric antigens, we investigated the response of murine bone marrow-derived dendritic cells to Gal-lectin and other amoebic components. We determined if immature DCs exposed to native Gal-lectin (1 µg/mL) or soluble amoebic proteins (20 µg/mL) undergo maturation changes and whether a Th1 response is induced. No maturation or cytokine induction was observed in DCs stimulated with soluble amoebic proteins. In contrast, incubation of immature DCs with Gal-lectin resulted in activation and maturation after 24 h. FACS analysis demonstrated an upregulation of DC maturation markers CD80, CD86, CD40 and MHCII upon exposure to Gal-lectin. The Gal-lectin also induced the production of IL-12 by DCs indicating a Th1 response. Gal-lectin activated DCs were able to stimulate T cell proliferation as measured by the allogeneic mixed leukocyte reaction in vitro. Adoptive transfer of Gal-lectin treated DCs into naïve mice resulted in IFN-
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta
Supported by NSERC