Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion

Abstract

Entamoeba histolytica, the causative agent of fatal diarrhoeal disease in children in the developing world, is shown here to kill human cells by biting off and ingesting pieces of cells, in a process reminiscent of the trogocytosis seen between immune cells; ingestion of bites is required for killing and this mechanism is used both in tissue culture and during invasion of intestinal explants. Entamoeba histolytica, the causative agent of fatal diarrhoeal disease in children in the developing world, was so named for its ability to destroy host tissues, although the mechanism underlying this effect was unclear. Here Katherine Ralston et al. describe how these amoeba kill intestinal epithelial cells by biting off and ingesting pieces of cell, in a process reminiscent of the trogocytosis seen between immune cells. Ingestion of the bites is required for killing, and the mechanism operates both in tissue culture and during invasion of intestinal explants. The authors suggest that intercellular exchange via trogocytosis may be more evolutionarily ancient and widespread than was assumed. This work also highlights amoebic trogocytosis as a potential target for new drugs to treat amoebiasis — a major neglected disease. Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrhoeal disease in the developing world. The parasite was named “histolytica” for its ability to destroy host tissues, which is probably driven by direct killing of human cells. The mechanism of human cell killing has been unclear, although the accepted model was that the parasites use secreted toxic effectors to kill cells before ingestion1. Here we report the discovery that amoebae kill by ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. After cell killing, amoebae detach and cease ingestion. Ingestion of human cell fragments is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of fragments of living human cells is reminiscent of trogocytosis (from Greek trogo, nibble) observed between immune cells2,3,4,5,6, but amoebic trogocytosis differs because it results in death. The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms7. These findings change the model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.