Functional Characterization of an Interferon Gamma Receptor-Like Protein on Entamoeba histolytica

Abstract

<i>Entamoeba histolytica</i> is an anaerobic parasitic protozoan and the causative agent of amoebiasis. <i>E. histolytica</i> expresses proteins that are structurally homologous to human proteins and uses them as virulence factors. We have previously shown that <i>E. histolytica</i> binds exogenous interferon gamma (IFN-γ) on its surface, and in this study, we explored whether exogenous IFN-γ could modulate parasite virulence. We identified an IFN-γ receptor-like protein on the surface of <i>E. histolytica</i> trophozoites by using anti-IFN-γ receptor 1 (IFN-γR1) antibody and performing immunofluorescence, Western blot, protein sequencing, and <i>in silico</i> analyses. Coupling of human IFN-γ to the IFN-γ receptor-like protein on live <i>E. histolytica</i> trophozoites significantly upregulated the expression of <i>E. histolytica</i> cysteine protease A1 (<i>Eh</i>CP-A1), <i>Eh</i>CP-A2, <i>Eh</i>CP-A4, <i>Eh</i>CP-A5, amebapore A (APA), cyclooxygenase 1 (<i>Cox-1</i>), Gal-lectin (<i>Hgl</i>), and peroxiredoxin (<i>Prx</i>) in a time-dependent fashion. IFN-γ signaling via the IFN-γ receptor-like protein enhanced <i>E. histolytica</i>'s erythrophagocytosis of human red blood cells, which was abrogated by the STAT1 inhibitor fludarabine. Exogenous IFN-γ enhanced chemotaxis of <i>E. histolytica</i>, its killing of Caco-2 colonic and Hep G2 liver cells, and amebic liver abscess formation in hamsters. These results demonstrate that <i>E. histolytica</i> expresses a surface IFN-γ receptor-like protein that is functional and may play a role in disease pathogenesis and/or immune evasion.