Activation of dendritic cells by the Gal-lectin of Entamoeba histolytica drives Th1 responses in vitro and in vivo.
Amebiasis is a human disease caused by the protozoan intestinal parasite Entamoeba histolytica. Vaccine development has focused on the parasite's surface galactose-N-acetyl-D-galactosamine inhibitable lectin (Gal-lectin) as a protective antigen. 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. In this study, we investigated the response of BALB/c bone marrow-derived DC to E. histolytica Gal-lectin. Incubation of immature DC with Gal-lectin resulted in activation and maturation after 24 h. FACS analysis demonstrated an up-regulation of DC maturation markers CD80, CD86, CD40 and MHC class II upon exposure to Gal-lectin. The Gal-lectin also induced DC production of IL-12, indicating a Th1 response. Gal-lectin-activated DC were able to stimulate T cell proliferation in an allogeneic mixed leukocyte reaction and adoptive transfer of Gal-lectin-treated DC into naïve mice resulted in IFN-gamma-producing Gal-lectin-sensitized T cells. The activation of DC by Gal-lectin was mediated by MAPK and NF-kappaB. These findings indicate that E. histolytica Gal-lectin is a potent vaccine antigen capable of directly initiating DC maturation and activation characterized by Th1 cytokine production.
Ivory
Catherine P A
CP
Faculty of Medicine, Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, Alberta, Canada.
Chadee
Kris
K
D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000469:parasitology*; D024202:Electrophoretic Mobility Shift Assay; D004748:Entamoeba histolytica / Q000276:immunology; D004749:Entamoebiasis / Q000276:immunology / Q000517:prevention & control*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D037102:Lectins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology
D037102:Lectins; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C078014:N-acetylgalactosamine inhibitable lectin 35-kDa subunit, Entamoeba histolytica; D018664:Interleukin-12; D048049:Extracellular Signal-Regulated MAP Kinases