Epithelial cell apoptosis facilitates Entamoeba histolytica infection in the gut.

Entamoeba histolytica is the protozoan parasite that causes amebic colitis. The parasite triggers apoptosis on contact with host cells; however, the biological significance of this event during intestinal infection is unclear. We examined the role of apoptosis in a mouse model of intestinal amebiasis. Histopathology revealed that abundant epithelial cell apoptosis occurred in the vicinity of amoeba in histological specimens. Epithelial cell apoptosis occurred rapidly on co-culture with amoeba in vitro as measured by annexin positivity, DNA degradation, and mitochondrial dysfunction. Administration of the pan caspase inhibitor ZVAD decreased the rate and severity of amebic infection in CBA mice by all measures (cecal culture positivity, parasite enzyme-linked immunosorbent assay, and histological scores). Similarly, caspase 3 knockout mice on the resistant C57BL/6 background exhibited even lower cecal parasite antigen burden and culture positive rates than wild type mice. The permissive effect of apoptosis on infection could be tracked to the epithelium, in that transgenic mice that overexpressed Bcl-2 in epithelial cells were more resistant to infection as measured by cecal parasite enzyme-linked immunosorbent assay and histological scores. We concluded that epithelial cell apoptosis in the intestine facilitates amebic infection in this mouse model. The parasite's strategy for inducing apoptosis may point to key virulence factors, and therapeutic maneuvers to diminish epithelial apoptosis may be useful in amebic colitis.

Entamoeba histolytica activates host cell caspases during contact-dependent cell killing.

Entamoeba histolytica is a human intestinal parasite that causes amoebic colitis as well as liver abscesses. Host tissues are damaged through a three-step process involving adherence, contact-dependent cytolysis, and phagocytosis. These three processes all contribute to the pathogenicity of this parasite. Adherence is provided by the Gal/GalNAc adherence lectin. Host cells are lysed in a contact-dependent fashion. There is evidence that suggests that this contact-dependent killing involves the induction of the host cell's apoptotic machinery. Phagocytosis can then occur, consistent with metazoan apoptotic clearance.

Autochthonous amoebiasis in institutionalized mentally-retarded patients: preliminary evaluation of isoenzyme patterns in three isolates.

Three autochthonous cases of Entamoeba histolytica infection in institutionalized mentally-retarded patients are reported. Isoenzyme analysis by starch-gel electrophoresis shows the pathogenicity of the three isolates: two belong to zymodeme II, and one to zymodeme XIX. The study shows that invasive E. histolytica strains occur in Italy and can be isolated from institutionalized oligophrenic patients.

Role of beta-glucuronidase, a lysosomal enzyme, in the pathogenesis of intestinal amoebiasis: an experimental study.

The role of beta-glucuronidase (BG), released by blood monocytes and Kupffer cells, in the pathogenesis of intestinal amoebiasis was studied. Guinea-pigs, infected intracaecally with Entamoeba histolytica, were killed 0, 3, 7, 14 and 21 d after infection. Enhanced levels of BG were observed in the cell lysates as well as supernatants of both blood monocytes and Kupffer cells in the infected animals, from the 3rd day after infection, as compared to those in controls. The rise in BG levels was more marked on 7 and 14 d after infection (P less than 0.001). The animal which survived for 21 d had lower levels of BG, though still significantly higher than those in controls (P less than 0.05). The animals with grade IV or V caecal scoring and on the verge of death had higher levels of beta-glucuronidase. A direct correlation was observed between the enzyme levels and severity of infection. It is postulated that acid hydrolases have a role in causing tissue damage during intestinal amoebiasis.

Biochemical homogeneity of Entamoeba histolytica isolates, especially those from liver abscess.

The electrophoretic mobility patterns of four enzymes from trophozoites of Entamoeba histolytica were examined to determine the zymodeme of the amoebae populations involved. E. histolytica populations from aspirated liver pus belonged exclusively to types II and XI of eighteen zymodemes. E. histolytica from cases of amoebic dysentery--i.e., those patients presenting with intestinal ulceration and/or with haematophagous trophozoites in the faeces--also belonged to zymodemes II and XI. However, symptom-free cyst passers harboured E. histolytica belonging to one of several zymodemes none of which corresponded wth the zymodemes of the patients with liver abscesses or amoebic dysentery.