Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion

Entamoeba histolytica is the causative agent of amoebiasis, a potentially fatal diarrheal disease in the developing world. The parasite was named “histolytica” for its ability to destroy host tissues, which is most likely driven by direct killing of human cells. The mechanism of human cell killing has been unclear, though the accepted model was that the parasites use secreted toxic effectors to kill cells prior to ingestion(1). Here we report the surprising discovery that amoebae kill by biting off and 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 bites is required for cell killing, and also contributes to invasion of intestinal tissue. The internalization of bites of living human cells is reminiscent of trogocytosis (Greek trogo–, nibble) observed between immune cells(2–6), but amoebic trogocytosis differs since 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 organisms(7). These findings change the paradigm for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.