HEMOLYSIN-POSITIVE ENTEROAGGREGATIVE AND CELL-DETACHING ESCHERICHIA-COLI STRAINS CAUSE ONCOSIS OF HUMAN MONOCYTE-DERIVED MACROPHAGES AND APOPTOSIS OF MURINE J774 CELLS

Infection of human monocyte-derived macrophages (HMDM) and J774 cells (murine macrophage cell line) with several enteroaggregative and cytod etaching Escherichia coli (EAggEC and CDEC, respectively) strains demo nstrated that some strains could induce macrophage cell death accompan ied by release of lactate dehydrogenase activity and interleukin 1 bet a (IL-1 beta) into culture supernatants. The mode of cell death differ ed in the two types of macrophages. Damage to macrophage plasma membra ne integrity without changes in nuclear morphology resulted in cytolys is of HMDM. This mechanism of cell death has been previously described for virulent Shigella infection of HMDM and is termed oncosis. In con trast, infection of J774 tells by EAggEC and CDEC strains resulted in apoptosis. The presence of alpha-hemolysin (Hly) in EAggEC and CDEC st rains appears to be critical for both oncosis in HMDM and apoptosis in J774 cells. Bacteria lacking Hly, including Hly(-) EAggEC strains as well as enterotoxigenic, enteropathogenic, and enterohemorrhagic E. co li strains, behaved like avirulent Shigella flexneri in that the macro phage monolayers were intact, with no release of lactate dehydrogenase activity or IL-1 beta into the culture supernatants.