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.
Author Summary Entamoeba histolytica is an intestinal parasite that causes amoebiasis, a potentially fatal diarrheal disease. Abscesses in organs outside of the intestine, such as the liver, can occur when amoebae are able to breach the intestinal wall and travel through the blood stream to other areas of the body. We previously showed that E. histolytica kills human cells by taking “bites” of human cell material in a process that we named trogocytosis (trogo-: nibble). Mammalian immune cells use trogocytosis to acquire proteins from other cells which impacts cell-cell communication. Here we tested the hypothesis that trogocytosis allows E. histolytica to acquire and display proteins from human cells allowing amoebae to survive in the blood stream. We demonstrate for the first time that through trogocytosis, E. histolytica acquires and displays human cell membrane proteins. We also demonstrate that trogocytosis of human cells allows amoebae to survive in human serum. These studies reveal a novel strategy for immune evasion by a pathogen and may apply to the pathogenesis of other infections.
