Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion.
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 ingestion. 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 cells, 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 organisms. These findings change the model for tissue destruction in amoebiasis and suggest an ancient origin of trogocytosis as a form of intercellular exchange.
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Katherine S
KS
Ralston
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.
Michael D
MD
Solga
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
Nicole M
NM
Mackey-Lawrence
School of Life Sciences, Jawaharlal Nehru University, 110067 New Delhi, India.
Somlata
School of Life Sciences, Jawaharlal Nehru University, 110067 New Delhi, India.
Alok
A
Bhattacharya
1] Department of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA [3] Department of Pathology, University of Virginia, Charlottesville, Virginia 22908, USA.
William A
WA
Petri
D005075:Biological Evolution; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D004748:Entamoeba histolytica / Q000166:cytology / Q000472:pathogenicity* / Q000502:physiology*; D004749:Entamoebiasis / Q000469:parasitology* / Q000473:pathology*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007422:Intestines / Q000469:parasitology* / Q000473:pathology*; D019169:Jurkat Cells; D058069:Neglected Diseases / Q000469:parasitology / Q000473:pathology
D002118:Calcium