April 28, 2014

Parasite Nibbles Human Cells to Death

Green cells surrounded by purple amoebas. An amoeba (green) nibbling off and engulfing pieces of a human cell (purple).Katherine Ralston

A diarrhea-causing parasite latches onto human cells and nibbles away at them until they die. The surprising finding—seen in live recordings of the cells in action—may lead to new ways to block the parasite, which causes up to 100,000 deaths worldwide each year.

The single-celled parasite Entamoeba histolytica is an amoeba that enters the human gut and produces an infection called amoebiasis. It’s most often seen in tropical regions with poor sanitation. Serious cases can lead to loose or bloody stools, stomach pain, and fever. The amoeba can cause extensive tissue damage, resulting in intestinal ulcers or deadly injury to other organs.

For years, scientists suspected that E. histolytica caused disease by poisoning and killing human cells before gobbling up the cellular corpses. But details of the lethal mechanism had been unclear.

To learn more, a team led by Drs. Katherine S. Ralston and William A. Petri, Jr., of the University of Virginia used advanced microscopy to watch as live parasites and host cells interacted with each other. The research was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results appeared in Nature on April 24, 2014.

The scientists fluorescently labeled the membranes of human immune cells. They then observed as amoebae attached to the cells and then bit away and engulfed tiny membrane fragments, one after another. Human cells remained intact for a while, despite the nibbling. But as their outer membrane eroded, the cells eventually died. The amoebae then abandoned the cellular corpses and moved on to their next live meal. When amoebae encountered pre-killed cells, they tended to swallow them whole instead of nibbling.

The researchers next paired amoebae with human red blood cells, since a hallmark of amoebiasis is finding traces of these cells inside amoebae. The amoebae attached to live cells and began nibbling, a process known as trogocytosis. Similar results occurred when the team paired amoebae with cells that line the human colon. Further experiments showed that once amoebae had engaged in trogocytosis, they became more voracious and efficient cell-killers.

To observe amoebae in action in a 3-D environment, the scientists incubated the parasites with mouse intestinal tissue. The amoebae navigated through tiny intestinal crevices. They then nibbled and killed the cells, penetrating deeper into the tissue. The team could block the tissue invasion with drugs that inhibit amoeba trogocytosis.

Trogocytosis had been seen before in immune cells, which use the process to exchange pieces of molecules that might be targeted in an immune attack. But this nibbling activity doesn’t destroy the immune cells.

“The findings suggest that amoebae might invade and destroy host intestinal tissue by nibbling alive the cells that line the gut,” Ralston says. “This is the first demonstration that nibbling can serve as a way to kill other cells.”

The researchers are continuing to explore ways to treat or prevent amoebiasis.

—by Vicki Contie


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References:  Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion. Ralston KS, Solga MD, Mackey-Lawrence NM, Somlata, Bhattacharya A, Petri WA Jr. Nature. 2014 Apr 24;508(7497):526-30. doi: 10.1038/nature13242. Epub 2014 Apr 9. PMID: 24717428.

Funding: NIH’s National Institute of Allergy and Infectious Diseases (NIAID); Howard Hughes Medical Institute; and Hartwell Foundation.