Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting enzyme (ICE) activity cause intestinal inflammation and tissue damage in amoebiasis

The protozoan parasite Entamoeba histolytica causes intestinal inflammation and ulceration. Amoebic trophozoites activate the transcription factor NF- kappa B in human intestinal epithelial cells, initiating an inflammatory re sponse programme with resultant damage to the intestinal tissue. Amoebic cy steine proteinases have been proposed as important virulence factors for am oebiasis. To test the role of amoebic cysteine proteinases in the pathogene sis of amoebic colitis, human intestinal xenografts in SCID mice were infec ted with E. histolytica trophozoites expressing an antisense message to ehc p5. The cysteine proteinase-deficient amoeba failed to induce intestinal ep ithelial cell production of the inflammatory cytokines interleukin (IL)-1B and IL-8, and caused significantly less gut inflammation and damage to the intestinal permeability barrier. The critical role of amoebic cysteine prot einases in human gut inflammation and tissue damage may be explained by our discovery that amoebic cysteine proteinases possess IL-1B converting enzym e (ICE) activity. This ICE activity could contribute to intestinal inflamma tion by activating human pIL-1B released by damaged intestinal cells. These results demonstrate for the first time that amoebic cysteine proteinases a re a key virulence factor in amoebic colitis, and provide a novel mechanism for their activity.