Trogocytosis by Entamoeba histolytica mediates acquisition and display of human cell membrane proteins and evasion of lysis by human serum

Abstract

Entamoeba histolytica is the protozoan parasite responsible for amoebiasis. We previously showed that E. histolytica kills human cells through a mechanism that we termed trogocytosis (trogo-: nibble), due to its resemblance to trogocytosis in other organisms. In parasites, trogocytosis is used to kill host cells. In multicellular organisms, trogocytosis is used for cell-cell interactions in the immune system, in the central nervous system, and during development. Thus, nibbling is an emerging theme in cell-cell interactions both within and between species, and it is relevant to host-pathogen interactions in many different contexts. When trogocytosis occurs between mammalian immune cells, cell membrane proteins from the nibbled cell can be acquired and displayed by the recipient cell. In this study, we tested the hypothesis that through trogocytosis of human cells, amoebae acquire and display human cell membrane proteins. Here we demonstrate for the first time that through trogocytosis, E. histolytica acquires and displays human cell membrane proteins and that this leads to protection from lysis by human serum. Protection from human serum only occurs after amoebae have undergone trogocytosis of live cells, but not phagocytosis of dead cells. Likewise, mutant amoebae that exhibit a phagocytosis defect, but are unaltered in their capacity to perform trogocytosis, are nevertheless protected from human serum. Our studies are the first to demonstrate that amoebae can display human cell membrane proteins and suggest that acquisition and display of membrane proteins is a general feature of trogocytosis that is not restricted to trogocytosis between mammalian immune cells. These studies have major implications for interactions between E. histolytica and the immune system and also reveal a novel strategy for immune evasion by a pathogen. Since other microbial eukaryotes use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections.