Caspase 3-dependent killing of host cells by the parasite Entamoeba histolytica

Abstract

SummaryThe parasite Entamoeba histolytica is named for its ability to lyse host tissues. To determine the factors responsible, we have initiated an examination of the contribution of parasite virulence factors and host caspases to cellular destruction by the parasite. Amoebic colitis in C3H/HeJ mice was associated with extensive host apoptosis at sites of E. histolytica invasion. In vitro studies of E. histolytica±Jurkat Tcell interactions demonstrated that apoptosis required contact via the amoebic Gal/GalNAc lectin, but was unaffected by 75% inhibition of the amoebic cysteine proteinases. Parasite-induced DNA fragmentation was unaffected in caspase 8-deficient Jurkat cells treated with the caspase 9 inhibitor Ac-LEHDfmk. In contrast, caspase 3-like activity was observed within minutes of E. histolytica contact and the caspase 3 inhibitor Ac-DEVD-CHO blocked Jurkat T cell death, as measured by both DNA fragmentation and 51 Cr release. These data demonstrate rapid parasite-induced activation of caspase 3-like caspases, independent of the upstream caspases 8 and 9, which is required for host cell death.

Resistance of C57BL/6 Mice to Amoebiasis Is Mediated by Nonhemopoietic Cells but Requires Hemopoietic IL-10 Production

“…The epithelium of IL-10 Ϫ/Ϫ mice exhibits defects in synthesis of Muc2 (23), a major component of human colonic mucus that limits E. histolytica adherence to host cells (32). Finally, the epithelium of IL-10 Ϫ/Ϫ mice can be predisposed toward increased apoptosis (14), and these cellular corpses could serve as fuel for the amoeba as happens in vitro (33,34). Another intriguing possibility is that trophozoites, being the tissue phase of the parasite, benefit from an IL-10-deficient proinflammatory state; for instance, TNF-␣ (though TNF message was not increased in Table I) is known to promote E. histolytica chemotaxis, adherence, and trophozoite-induced epithelial damage (6,35,36).…”

Identification of Trichomonas vaginalis Cysteine Proteases That Induce Apoptosis in Human Vaginal Epithelial Cells

“…Caspase-3 plays an important role in mediating the various morphological changes associated with Fas-mediated apoptosis (49). Caspase-3 activation has been implicated in apoptotic cell death induced by E. histolytica parasites in Jurkat cells (46,47) and mosquito mid-gut epithelial cells infected by the P. falciparum parasite (50). Recently, we also reported the activation of caspase-3 in T. foetus CP30-induced apoptosis in BVECs and BUECs (33,51).…”

“…There are a few published reports that show that parasitic pathogens, e.g. Acanthamoeba histolytica (41), Plasmodium falciparum (42), Trypanosoma cruzi (43), Cryptosporidium parvum (44), Toxoplasma gondii (45), and Entamoeba histolytica (46), can kill mammalian cells by an apoptotic mechanism that occurs in response to infection. However, the precise mechanisms by which individual pathogens induce cell death in specific host cells remain to be elucidated.…”

“…It can be expected that the mechanism(s) by which extracellular parasites, including T. vaginalis, induce host cell apoptosis are very likely to be quite different from the mechanism(s) used by intracellular parasites. CPs have been shown to be essential for E. histolytica-induced pathology, where they destroy host tissue (46,47).…”

Trophozoites ofEntamoeba histolyticaepigenetically silenced in several genes are virulence-attenuated

“…E. histolytica trophozoites can also kill mammalian cells by induction of programmed cell death (apoptosis). Host-cell apoptosis is detected in amoebic liver-abscess and intestinal disease in mice, suggesting that human intestinal epithelial or liver cells might undergo the same fate (Seydel & Stanley, 1998;Ragland et al, 1994;Huston et al, 2000;Boettner & Petri, 2005). Other factors that also play an important role in pathogenesis are the parasite secreted cysteine proteases (Que & Reed, 2000;Helberg, et al, 2001).…”