Entamoeba histolytica Trophozoites Interact with the c-Met Receptor at the Surface of Liver Origin Cells through the Gal/GalNAc Amoebic Lectin

Abstract

Amoebiasis in humans is caused by the protozoan parasite Entamoeba histolytica, which cytotoxic activity has been demonstrated on a wide variety of target cells. The process involves the adherence of the parasite to the cell, and such adherence is mediated by an amoebic surface lectin, known as Gal/GalNAc lectin. It is composed of heavy, intermediate, and light subunits. The carbohydrate recognition domain (CRD) has been identified within a cysteine-rich region in the lectin heavy subunit and has an amino acid sequence identity to the receptor-binding domain of hepatocyte growth factor (HGF). Recombinant CRD has been previously shown to compete with HGF for binding to the c-Met receptor IgG fusion protein. In the present study, we searched for evidence of interaction between the Gal/GalNAc lectin at the surface of trophozoites with the c-Met receptor expressed at the surface of HepG2 in coculture assays. Immunoprecipitation of the coculture lysate indicated interaction of the c-Met with a 60 kDa peptide recognized by antiamoebic lectin antibody. Colocalization of both molecules was detected by fluorescence confocal microscopy. Incubation of HepG2 cells with HGF before coculture with trophozoites prevents the cytotoxic effect caused by the parasites but not their adherence to the cells. Our results point to Gal/GalNAc lectin as a ligand of the c-Met receptor at the surface of HepG2 cells.

Immunomodulatory effect of extracellular vesicles from Entamoeba histolytica trophozoites: Regulation of NETs and respiratory burst during confrontation with human neutrophils

“…On the other hand, the induction of signaling by Gal-lectin through TLRs 2 and 4 has been reported in human colonic cells and in macrophages -activating the inflammasome in the latter-, so this amoebic molecule can be considered as a genuine PAMP and signaling promoter ( Kammanadiminti et al., 2004 ; Galván-Moroyoqui et al., 2011 ; Mortimer et al., 2014 ). It has recently been reported that Gal-lectin can also act as a ligand for the c-Met receptor on the surface of HepG2 cells, and that its occupancy by its natural ligand hepatocyte growth factor, prevents cytotoxic damage to liver cells due to the amoeba, without affecting its adherence ( Pérez-Hernández et al., 2021 ). Regarding E. histolytica calreticulin, this protein has been found in cytoplasmic vesicles of different sizes (which is in accordance with its presence in the EVs reported here) as well as on the surface of the parasite, and it is relocated in the phagocytic cups when the amoeba ingests red blood cells, in addition to transferring and joining apoptotic lymphocytes and human C1q ( González et al., 2011 ; Vaithilingam et al, 2012 ).…”

Entamoeba histolytica: Membrane and Non-Membrane Protein Structure, Function, Immune Response Interaction, and Vaccine Development

“…The molecular weight of this protein is 260 kDa, and all E. histolytica strains express this protein on their surface [26]. Structurally, this protein is a heterotrimer composed of heavy (Hgl), intermediate (Igl), and light (Lgl) subunits [27][28][29]. The Hgl and Lgl are covalently attached to each other and interact non-covalently with the Igl.…”