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

The parasite Entamoeba histolytica is named for its ability to lyse host ti ssues. To determine the factors responsible, we have initiated an examinati on of the contribution of parasite virulence factors and host caspases to c ellular destruction by the parasite. Amoebic colitis in C3H/HeJ mice was as sociated with extensive host apoptosis at sites of E. histolytica invasion. In vitro studies of E. histolytica-Jurkat T-cell 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 cel ls treated with the caspase 9 inhibitor Ac-LEHD-fmk. In contrast, caspase 3 -like activity was observed within minutes of E. histolytica contact and th e caspase 3 inhibitor Ac-DEVD-CHO blocked Jurkat T cell death, as measured by both DNA fragmentation and Cr-51 release. These data demonstrate rapid p arasite-induced activation of caspase 3-like caspases, independent of the u pstream caspases 8 and 9, which is required for host cell death.