ENTAMOEBA-HISTOLYTICA INDUCES HOST-CELL DEATH IN AMEBIC LIVER-ABSCESSBY A NON-FAS-DEPENDENT, NONTUMOR NECROSIS FACTOR ALPHA-DEPENDENT PATHWAY OF APOPTOSIS

Amebic liver abscess is characterized by extensive areas of dead hepat ocytes that form cavities surrounded by a thin rim of inflammatory cel ls and few Entamoeba histolytica trophozoites. E. histolytica produces pore-forming proteins and proteinases, but how trophozoites actually kill host cells has been unclear. Here, we report that E. histolytica induces apoptosis in both inflammatory cells and hepatocytes in a seve re combined immunodeficient (SCID) mouse model of amebic liver abscess . By studying infection in C57/BL6.lpr and C57/BL6.gld mice, we found that E. histolytica-induced apoptosis does not require the Fas/Fas lig and pathway of apoptosis, and by using mice with a targeted deletion o f the tumor necrosis factor receptor I gene, we have shown that E. his tolytica-induced apoptosis is not mediated by tumor necrosis factor al pha. Our data indicate that apoptosis plays a prominent role in the ho st cell death seen in amebic liver abscess in a mouse model of disease and suggest that E. histolytica induces cell death without using two common pathways for apoptosis.