Monday 2 September, 1:00pm
Biochemistry Seminar Room BIG13
Dr Katherine Ralston
Department of Microbiology and Molecular Genetics, University of California, Davis
Chew on this: trogocytosis by Entamoeba histolytica enables human cell killing and immune evasion
Entamoeba histolytica is a pathogenic amoeba and the causative agent of the diarrheal disease amoebiasis in humans. It was named “histolytica” for the capacity to invade and damage host tissues. E. histolytica trophozoites (“amoebae”) can cause ulceration of the large intestine and can disseminate to cause fatal abscesses in other tissues. Little is known of the mechanisms that drive pathogenesis. Amoebae can kill human cells, but the mechanism was previously unclear. We established a new paradigm by discovering that amoebae kill human cells by biting off and ingesting fragments, which we call “amoebic trogocytosis” (trogo-: nibble). We subsequently found that amoebae display human cell membrane proteins after performing trogocytosis and become protected from lysis by human complement. We are now delineating this unexpected and novel strategy for immune evasion. We are applying imaging flow cytometry, host and amoeba mutants, and a variety of host cell types to dissect the contribution of trogocytosis to immune avoidance in vitro, and we are using the mouse model of amoebiasis to extend these findings to pathogenesis in vivo. Beyond E. histolytica, trogocytosis is a burgeoning theme that has far-reaching applications to eukaryotic biology. Several microbial eukaryotes use trogocytosis to kill other cells. In multicellular eukaryotes, trogocytosis is used for cell-killing, cell-cell communication and cell-cell remodeling. Trogocytosis plays roles in the immune system, in the central nervous system, and during development. Therefore, an improved understanding of the mechanism and biology of E. histolytica trogocytosis will apply both directly to the pathogenesis of amoebiasis and broadly to eukaryotic trogocytosis in general.
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