UC Davis

Trogocytosis is an endocytic process that is present in many eukaryotes including multicellular organisms and unicellular microbes. Paradoxically, it can be used as a benign form of cell-cell interaction, and it can also be used as a mechanism for cell-mediated killing. Trogocytosis is characterized by ingestion of small pieces of living cells. Additionally, in mammalian immune cells, and in the pathogen Entamoeba histolytica, trogocytosis results in the transfer of membrane proteins from one cell to another. Here, we give a broad overview of trogocytosis, its functions, and proposed molecular mechanisms in different cell types. These studies also reveal trogocytosis as a novel immune evasion mechanism employed by E. histolytica, the parasite responsible for the diarrheal disease amoebiasis. We demonstrate that E. histolytica displays human proteins after performing trogocytosis on human cells, and that this leads to protection from complement lysis. Trophozoites (amoebae) are protected from complement lysis following trogocytosis of live cells but not phagocytosis of dead cells. Amoebic trogocytosis leads to decreased deposition of the complement protein C3b. Furthermore, amoebae acquire and display human CD59 and CD46, which are known negative regulators of the complement pathway. While deletion of one or two complement regulatory proteins from human cells was not sufficient to alter conferred protection, amoebae mutants that exogenously expressed human CD46 or CD55 were protected from lysis. Thus, surface display of an individual negative regulator of complement is sufficient to protect amoebae from lysis. These findings indicate that amoebae likely acquire multiple redundant complement regulators from trogocytosis of human cells which leads to robust protection from complement lysis. Finally, we developed an assay to quantify trogocytosis in mammalian immune cells and generated mutant amoebae trogocytosis and phagocytosis defects. These tools can be used for future study of this important eukaryotic process.