Ready when you are, intestinal cell. These words, which echo an exchange between Hannibal Lecter and the ill-fated Sergeant Pembry, could be attributed to Entamoeba histolytica, an amoeba that bites into host cells and wears some of the leftovers. By displaying its host’s cell membrane proteins, the amoeba camouflages itself and evades immune detection.
According to scientists based at the University of California, Davis, the amoeba isn’t limited to phagocytosis, the engulfing of target cells on its menu. It can also pinch off small pieces of human cells, a process that the scientists liken to trogocytosis. (“Trogo-” means “nibble.”) Trogocytosis is an emerging theme in cell-cell interactions both within and between species. It pertains no only to cell killing, but also to cell-cell communications—and sometimes, both.
“The amoeba quite literally takes bites out of other cells,” said Katherine S. Ralston, an assistant professor of microbiology and molecular genetics. “This nibbling is how it attacks individual cells, and we think this is how it causes ulceration and damage to the human intestine.”
Cell nibbling has also been described in other parasitic amoebae—and also in multicellular organisms. Immune system cells, for example, can swap pieces of their surface with each other by biting them off.
“We thought that if amoebae can take proteins from host cells and put them on their own surface this would have a functional effect on how they survive in the body,” added graduate student Hannah W. Miller.
Hannah Miller is the first author of an article (“Trogocytosis by Entamoeba histolytica Mediates Acquisition and Display of Human Cell Membrane Proteins and Evasion of Lysis by Human Serum”) that appeared April 30 in mBio. This article presents evidence that E. histolytica uses trogocytosis to protect itself from lysis by human serum.
“Our studies are the first to reveal that amoebae can display human cell membrane proteins and suggest that the acquisition and display of membrane proteins is a general feature of trogocytosis,” the article’s authors wrote. “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.”
E. histolytica causes severe diarrheal disease, mainly in tropical countries. It lives in the gut, causing ulcers and bleeding. In severe cases it can break out and invade other organs.
This amoeba’s nibbling behavior has also been described in other parasitic amoebae—and also in multicellular organisms. Immune system cells, for example, can swap pieces of their surface with each other by biting them off.
By studying the amoeba’s nibbling behavior, Ralston and colleagues may have revealed a novel strategy for immune evasion by a pathogen and may apply to the pathogenesis of other infections.
The body produces a set of proteins in the blood, called “complement,” that can attack parasites and bacteria. Your own cells carry proteins that prevent them from being attacked by complement.
Ralston and colleagues found that when the amoebae were put in contact with human cells, the single-celled organisms could take these protective proteins and put them on as a sort of “complement camouflage.” Regular Entamoebae were killed by human serum, but amoebae that had camouflaged themselves survived.
This camouflage could protect them from complement as they migrate through the blood around the body, Miller indicated.
Ralston’s team is now working to understand which proteins are transferred, how they interact with complement and what happens to these proteins after they are nibbled off another cell. Do they go straight into the amoeba’s membrane, or are they processed internally first?
The team also wants to know more about trogocytosis in general. Why are some cases benign, but others lead to cell death? The process may also be important for understanding behavior of cancer cells and how they can be killed.
“We’re really excited that this decoration with acquired proteins might apply to trogocytosis in general, because we’re realizing that it’s important in so many contexts,” Ralston emphasized.