Human liver sinusoidal endothelial cells respond to interaction with Entamoeba histolytica by changes in morphology, integrin signalling and cell death

Unité Biologie Cellulaire du Parasitisme, Institut Pasteur, Paris, France.
Cellular Microbiology (Impact Factor: 4.92). 07/2011; 13(7):1091-106. DOI: 10.1111/j.1462-5822.2011.01604.x
Source: PubMed


Invasive infection with Entamoeba histolytica causes intestinal and hepatic amoebiasis. In liver, parasites cross the endothelial barrier before abscess formation in the parenchyma. We focussed on amoebae interactions with human hepatic endothelial cells, the latter potentially playing a dual role in the infection process: as a barrier and as modulators of host defence responses. We characterized early responses of a human liver sinusoidal endothelial cell line to virulent and virulence-attenuated E. histolytica. Within the first minutes human cells start to retract, enter into apoptosis and die. In the presence of virulent amoebae, expression of genes related to cell cycle, cell death and integrin-mediated adhesion signalling was modulated, and actin fibre, focal adhesion kinase and paxillin localizations changed. Effects of inhibitors and amoeba strains not expressing pathogenic factors amoebapore A and cysteine protease A5 indicated that cell death and cytoskeleton disorganization depend upon parasite adhesion and amoebic cysteine proteinase activities. The data establish a relation between cytotoxic effects of E. histolytica and altered human target cell adhesion and suggest that interference with adhesion signalling triggers endothelial cell retraction and death. Understanding the roles of integrin signalling in endothelial cells will provide clues to unravel host-pathogen interactions during amoebic liver infection.

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Available from: Anne Danckaert, Jan 07, 2015
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    • "To analyze the potential dominant-negative phenotype of KCS on the known functions of KERP1, parasites expressing KCS were incubated with human enterocytic (Caco2 line) or liver sinusoidal endothelial (LSEC line) cell monolayers. Previous work has shown the ability of E. histolytica to adhere and kill LSEC1617 and Caco2 cells218. For adherence assays, trophozoites were left to interact with the host cells for 30 minutes, allowing parasite adhesion with a reduced destruction of the monolayer. "
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