title: Human liver sinusoidal endothelial cells respond to interaction with Entamoeba histolytica by changes in morphology, integrin signalling and cell death.
abstract: 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.
authors.affiliation: Unité Biologie Cellulaire du Parasitisme, Institut Pasteur, Paris, France. daniela.faust@pasteur.fr
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Faust
authors.forename: Jacques
authors.initials: J
authors.lastname: Marquay Markiewicz
authors.forename: Anne
authors.initials: A
authors.lastname: Danckaert
authors.forename: Guillaume
authors.initials: G
authors.lastname: Soubigou
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillen
mesh_terms: D002448:Cell Adhesion; D016923:Cell Death; D002460:Cell Line; D057056:Cysteine Proteases / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000469:parasitology*; D004748:Entamoeba histolytica / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D008099:Liver / Q000469:parasitology*; D046228:Microarray Analysis; D008853:Microscopy; D015800:Protozoan Proteins / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D016023:Integrins; D007473:Ion Channels; D015800:Protozoan Proteins; D037521:Virulence Factors; C041670:amoebapore proteins, protozoan; D057056:Cysteine Proteases