The gal-lectin in host defence against entamoeba histolytica

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Entamoeba histolytica is a parasitic protozoan that causes the disease amebiasis characterized by bloody dysentery and liver abscess. About 1% of the world's population carries the parasite, resulting in 50 million cases of invasive disease and 100,000 deaths per year. It is among the 10 leading causes of mortality worldwide. At present, it is not known why the parasites are not controlled during infection. However, patients who are drug-cured are resistant to reinvasion suggesting that protective immunity occurs. Clinical and experimental studies indicate that cell-mediated immunity mediated by macrophages (the white blood cells that kill the parasites) is important in control and resistance to re-infection. Thus, a priority to the control of amebiasis is to develop a safe and effective vaccine. The major surface molecule on the parasite involved in the initiation of disease is the galactose-binding protein called the Gal-lectin. This protein is immunodominant and is recognized by serum from patients who had/has the disease. Immunization of animals with the Gal-lectin protected them against a challenge infection suggesting it is a good vaccine candidate molecule against amebiasis. However, it is not known what portion(s) of the Gal-lectin elicits the protective immune response. We hypothesized that specific portions of the Gal-lectin stimulates cell-mediated immunity for host defense against the disease. Accordingly, the specific aims of this study are: (1) to identify the critical regions of the Gal-lectin that stimulate innate and adaptive immune responses and, (2) to identify the host cell receptor and the signaling events involved in protective immunity. Our strategy is to first fine map the protective epitopes of the Gal-lectin using a panel of monoclonal antibodies that recognize distinct domains. Secondly, we will identify the receptors on dendritic cells that stimulate a protective immune response by using cells and animals that are deficient in the putative receptor(s) for the Gal-lectin. Characterizing the receptor and the signaling events involved in stimulating the right immune response is important in developing strategies to enhance vaccine development against this devastating disease.