Roles of cell adhesion and cytoskeleton activity in Entamoeba histolytica pathogenesis: a delicate balance.
The protozoan parasite Entamoeba histolytica colonizes the human large bowel. Invasion of the intestinal epithelium causes amoebic colitis and opens the route for amoebic liver abscesses. The parasite relies on its dynamic actomyosin cytoskeleton and on surface adhesion molecules for dissemination in the human tissues. Here we show that the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin clusters in focal structures localized in the region of E. histolytica that contacts monolayers of enterocytes. Disruption of myosin II activity impairs the formation of these structures and renders the trophozoites avirulent for liver abscess development. Production of the cytoplasmic domain of the E. histolytica Gal/GalNAc lectin in engineered trophozoites causes reduced adhesion to enterocytes. Intraportal delivery of these parasites to the liver leads to the formation of a large number of small abscesses with disorganized morphology that are localized in the vicinity of blood vessels. The data support a model for invasion in which parasite motility is essential for establishment of infectious foci, while the adhesion to host cells modulates the distribution of trophozoites in the liver and their capacity to migrate in the hepatic tissue.
Tavares
Paulo
P
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France. tavares@vms.cnrs-gif.fr
Rigothier
Marie-Christine
MC
Khun
Huot
H
Roux
Pascal
P
Huerre
Michel
M
Guillén
Nancy
N
D000818:Animals; D002448:Cell Adhesion; D006224:Cricetinae; D003599:Cytoskeleton / Q000378:metabolism*; D004748:Entamoeba histolytica / Q000472:pathogenicity* / Q000502:physiology*; D004749:Entamoebiasis / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D020895:Enterocytes / Q000469:parasitology; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008101:Liver Abscess, Amebic / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D009218:Myosins / Q000378:metabolism; D014774:Virulence
D037102:Lectins; D009218:Myosins
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