The role of cytokines in host defence against Entamoeba histolytica /

Entamoeba histolytica is a protozoan parasite and the causative agent of amoebiasis. While infection is associated with suppression of cell-mediated, immunity, drug-cured patients are resistant to reinvasion by amoebae. Macrophages are the principal effector cells in host defence against E. histolytica via production of nitric oxide which is cytotoxic for the parasite. The objective of this study was to determine the T cell cytokine responses associated with host defence against E. histolytica . A mixed Th1/Th2 (Th0) response predominated at days 5--10 of amoebic liver abscess development in gerbils, as indicated by spleen and hepatic lymph node cell IL-2 (Th1 marker) and IL-4 (Th2 marker) production. However, T cell responses were profoundly suppressed at day 20 of infection. Serum collected at day 20, but not at other times, markedly suppressed T cell proliferative responses by inhibiting IL-2 production. A switch to a Th1 response occurred after day 20 of infection. Following drug-abbreviation of infection at day 20, animals were completely resistant to challenge infection in the liver and demonstrated a Th1 response. The Gal-lectin 170-kDa heavy subunit of E. histolytica is a protective antigen in gerbils and a potential subunit vaccine candidate. We determined which region of the Gal-lectin stimulates IL-12 production, as IL-12 is key to inducing Th1 cytokine responses. Native Gal-lectin plus interferon-gamma stimulated IL-12 p40 and p35 gene transcription and IL-12 p70 protein production in human macrophages. Using a panel of anti-170-kDa subunit monoclonal antibodies in inhibition studies, aa 596--998 was identified as the IL-12-inducing domain. These results suggest that this portion of the Gal-lectin has potential for use as a subunit vaccine to induce Th1-mediated immunity against E. histolytica