Initiation of inflammation and cell death during liver abscess formation by Entamoeba histolytica depends on activity of the galactose/N-acetyl-D-galactosamine lectin.
The parasite Entamoeba histolytica colonizes the human intestine causing amoebic colitis and disseminates through the vascular route to form liver abscesses. The Gal/GalNAc lectin is an adhesion protein complex which sustains tissue invasion by E. histolytica. Disruption of the Gal/GalNAc lectin function in engineered parasites (HGL-2 trophozoites) changed the pathophysiology of hamster liver abscess formation. HGL-2 trophozoites produced numerous small inflammatory foci located in the vicinity of blood vessels. The low penetration of HGL-2 trophozoites into hepatic tissue was shown to be associated with weak attraction of neutrophils and macrophages to the infiltrated areas and absence of pro-inflammatory tumour necrosis factor, in contrast to wild type or control vector infections. The low host inflammatory response in HGL-2 infections correlated with a delay in apoptosis of hepatic cells, whereas apoptosis of endothelial cells was not detected. Triggering of apoptosis in both host cell types most likely has a central role in modulating inflammation, a major landmark in hepatic amoebiasis. These data highlight the key role of the Gal/GalNAc lectin in initiation of E. histolytica hepatic infection.
Blazquez
Samantha
S
Institut Pasteur, Unité de Biologie Cellulaire du Parasitisme, Paris, F-75015, France.
Rigothier
Marie-Christine
MC
Huerre
Michel
M
Guillén
Nancy
N
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D006224:Cricetinae; D004195:Disease Models, Animal; D004748:Entamoeba histolytica / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D022781:Hepatocytes / Q000473:pathology; D006790:Host-Parasite Interactions; D037102:Lectins / Q000502:physiology*; D008101:Liver Abscess, Amebic / Q000276:immunology / Q000469:parasitology* / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology; D008297:Male; D008647:Mesocricetus; D011971:Receptors, Immunologic / Q000378:metabolism*; D053058:Trophozoites / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014774:Virulence
D037102:Lectins; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C037045:galactose-N-acetylgalactosamine receptor