Functional Characterization Of An Interferon Gamma Receptor-Like Protein On Entamoeba Histolytica

Entamoeba histolytica is an anaerobic parasitic protozoan and the causative agent of amoebiasis. E. histolytica expresses proteins that are structurally homologous to human proteins and uses them as virulence factors. We have previously shown that E. histolytica binds exogenous interferon gamma (IFN-gamma) on its surface, and in this study, we explored whether exogenous IFN-gamma could modulate parasite virulence. We identified an IFN-gamma receptor-like protein on the surface of E. histolytica trophozoites by using anti-IFN-gamma receptor 1 (IFN-gamma R1) antibody and performing immunofluorescence, Western blot, protein sequencing, and in silico analyses. Coupling of human IFN-gamma to the IFN-gamma receptor-like protein on live E. histolytica trophozoites significantly upregulated the expression of E. histolytica cysteine protease A1 (EhCP-A1), EhCP-A2, EhCP-A4, EhCP-A5, amebapore A (APA), cyclooxygenase 1 (Cox-1), Gal-lectin (Hgl), and peroxiredoxin (Prx) in a time-dependent fashion. IFN-gamma signaling via the IFN-gamma receptor-like protein enhanced E. histolytica's erythrophagocytosis of human red blood cells, which was abrogated by the STAT1 inhibitor fludarabine. Exogenous IFN-gamma enhanced chemotaxis of E. histolytica, its killing of Caco-2 colonic and Hep G2 liver cells, and amebic liver abscess formation in hamsters. These results demonstrate that E. histolytica expresses a surface IFN-gamma receptor-like protein that is functional and may play a role in disease pathogenesis and/or immune evasion.