Entamoeba histolytica Gal/GalNAc lectin intermediate subunit as a potential driver of inflammation and epithelial...

Entamoeba histolytica is a common enteric protozoan that sometimes transitions from a symbiont to a pathogen, causing intestinal amebiasis and extraintestinal abscesses in the host. The early-to-intermediate stages of intestinal amebiasis are characterized by an intense inflammatory response. Here, using the cecal infection model of C3H/HeNCrl mice, we performed single-cell RNA sequencing of cecal tissues and identified the prominent pro-inflammatory function of host macrophages in intestinal amebiasis. On the amebic cell surface, Igl is the intermediate subunit of galactose- and N-acetyl-D-galactosamine-inhibitable lectins, which contributes to parasite adherence. We proposed a potential mechanism whereby E. histolytica Igl diffuses along with amebic extracellular vesicles and contacts host macrophages, presumably binding to the TLR4 co-receptor MD2 through its C3 region and initiating the TLR4/MyD88/NF-κB inflammatory signaling pathway in host cells. Moreover, by inducing macrophage inflammation and cytokine production, E. histolytica appears to indirectly compromise intestinal epithelium integrity through the Igl protein. To our knowledge, this is the first report showing a host single-cell atlas in the field of amebiasis research. In response to the parasite invasion during intestinal amebiasis, our study yields additional clues elucidating the inflammatory formation and epithelial damage of gut mucosal immune system, and may contribute to the identification of potential drug targets for these amebas.