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Infect Immun, August 1998, p. 3918-3924, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Hemolysin-Positive Enteroaggregative and Cell-Detaching Escherichia coli Strains Cause Oncosis of Human Monocyte-Derived Macrophages and Apoptosis of Murine J774 Cells

Carmen Fernandez-Prada,1 Ben D. Tall,2 Simon E. Elliott,3 David L. Hoover,1 James P. Nataro,3 and Malabi M. Venkatesan1 *

Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 203071; Microbial Ecology Branch, CFSAN, Food and Drug Administration, Washington, D.C. 202042; and Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 212013

Received 10 February 1998/Returned for modification 19 March 1998/Accepted 27 May 1998

Infection of human monocyte-derived macrophages (HMDM) and J774 cells (murine macrophage cell line) with several enteroaggregative and cytodetaching Escherichia coli (EAggEC and CDEC, respectively) strains demonstrated that some strains could induce macrophage cell death accompanied by release of lactate dehydrogenase activity and interleukin 1beta (IL-1beta ) into culture supernatants. The mode of cell death differed in the two types of macrophages. Damage to macrophage plasma membrane integrity without changes in nuclear morphology resulted in cytolysis of HMDM. This mechanism of cell death has been previously described for virulent Shigella infection of HMDM and is termed oncosis. In contrast, infection of J774 cells by EAggEC and CDEC strains resulted in apoptosis. The presence of alpha -hemolysin (Hly) in EAggEC and CDEC strains 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. coli strains, behaved like avirulent Shigella flexneri in that the macrophage monolayers were intact, with no release of lactate dehydrogenase activity or IL-1beta into the culture supernatants.

* Corresponding author. Mailing address: Department of Enteric Infections, Bldg. 40, Room B020, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100. Phone: (202) 782-6236. Fax: (202) 782-3299. E-mail: dr._malabi_venkatesan{at}wrsmtp-ccmail.army.mil.

Infect Immun, August 1998, p. 3918-3924, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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