The dynamic interplay of human cells and Entamoeba histolytica during trogocytosis (cell-nibbling)

Entamoeba histolytica is a pathogenic amoeba and the causative agent of amoebiasis in humans. Despite its impact on human health, E. histolytica is dramatically understudied. The species name (histo-: tissue; lytic-: dissolving) derives from the ability to destroy host tissues. E. histolytica trophozoites (“amoebae”) invade the large intestine, causing ulceration and can enter the bloodstream, and they can disseminate to disseminate to other tissues, causing fatal abscesses. Little is known of the mechanisms that allow E. histolytica to damage the intestine. We established a new paradigm by discovering that amoebae attack and kill human cells by biting off and ingesting human cell fragments, which we named “amoebic trogocytosis” (trogo-: nibble) (Ralston, et al., Nature, 2014). Since trogocytosis occurs in many other eukaryotes, this process may be fundamental to eukaryotic cell biology. However, the mechanistic differences between eukaryotic trogocytosis and phagocytosis (ingestion of entire cells) are unclear, as are the signals that initiate each process. When amoebae are incubated with live human cells, they take bites, but when amoebae are incubated with dead human cells, they eat the entire cells. This suggests that either live human cells play an active role in trogocytosis, or that physical properties of live cells, such as deformability, are necessary. Building on the discovery of amoebic trogocytosis, we propose to further delineate the interplay between the amoeba and human cell, and what about this interplay leads the amoeba to perform trogocytosis vs. phagocytosis. Beyond E. histolytica, trogocytosis is a burgeoning theme with has far-reaching applications to eukaryotic biology. Several microbes use trogocytosis to kill other cells, including the “brain-eating” amoeba Naegleria fowleri. In multicellular eukaryotes, trogocytosis is used for cell-killing, cell-cell communication and cell-cell remodeling, and it plays roles in the immune system, the central nervous system, and during development. 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. This work is significant and high-impact as it will improve understanding of trogocytosis, a process that is changing the paradigm for amoebiasis pathogenesis. New understanding of the interplay between cells during trogocytosis will also apply broadly to eukaryotic trogocytosis in general. Project Number: 1R21AI193905-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Katherine Ralston | Institution: UNIVERSITY OF CALIFORNIA AT DAVIS, DAVIS, CA | Award Amount: $431,004 | Activity Code: R21 | Study Section: Pathogenic Eukaryotes Study Section[PTHE] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R21AI19390501