Figure 11.

Working model of E. histolytica damage on epithelium focused on EhCP112 action. Trophozoites secrete different molecules (PGE₂ and cystein proteases) to cross the mucin layer and reach the epithelium. Then, trophozoites adhere to epithelial cells by specific molecules (Gal/GalNAc, EhADH, and others). EhCP112 reaches the intercellular space, selectively affecting claudin-1 and claudin-2, but not claudin-4, occludin, ZO-1 and ZO-2 that are damaged by other trophozoites molecules. TJs are disrupted, affecting gate and fence functions. Then, EhCP112 moves to AJs and DSMs. The cell-cell contact is lost and epithelial cells detach, facilitating the invasion by trophozoites. Alternatively, EhCP112 is internalized to the cell by caveolae and clathrin coated pits, contributing to epithelial damage through protein degradation.