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Infection and Immunity, August 2001, p. 4923-4930, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.4923-4930.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Escherichia coli Enterotoxin B Subunit Triggers Apoptosis of CD8+ T Cells by Activating Transcription Factor c-Myc

Marco Soriani, Neil A. Williams, and Timothy R. Hirst*

Department of Pathology and Microbiology, University of Bristol, Bristol, BS8 1TD, United Kingdom

Received 20 February 2001/Returned for modification 10 April 2001/Accepted 11 May 2001

Heat-labile enterotoxin from enterotoxinogenic Escherichia coli is not only an important cause of diarrhea in humans and domestic animals but also possesses potent immunomodulatory properties. Recently, the nontoxic, receptor-binding B subunit of heat-labile enterotoxin (EtxB) was found to induce the selective death of CD8+ T cells, suggesting that EtxB may trigger activation of proapoptotic signaling pathways. Here we show that EtxB treatment of CD8+ T cells but not of CD4+ T cells triggers the specific up-regulation of the transcription factor c-myc, implicated in the control of cell proliferation, differentiation, and death. A concomitant elevation in Myc protein levels was also evident, with peak expression occurring 4 h posttreatment. Preincubation with c-myc antisense oligodeoxynucleotides demonstrated that Myc expression was necessary for EtxB-mediated apoptosis. Myc activation was also associated with an increase of Ikappa Balpha turnover, suggesting that elevated Myc expression may be dependent on NF-kappa B. When CD8+ T cells were pretreated with inhibitors of Ikappa Balpha turnover and NF-kappa B translocation, this resulted in a marked reduction in both EtxB-induced apoptosis and Myc expression. Further, a non-receptor-binding mutant of EtxB, EtxB(G33D), was shown to lack the capacity to activate Myc transcription. These findings provide further evidence that EtxB is a signaling molecule that triggers activation of transcription factors involved in cell survival.

* Corresponding author. Mailing address: Department of Pathology and Microbiology, University of Bristol, Bristol, BS8 1TD, United Kingdom. Phone: 44 0117 9287538. Fax: 44 0117 930 0543. E-mail: t.r.hirst{at}bristol.ac.uk.

Infection and Immunity, August 2001, p. 4923-4930, Vol. 69, No. 8
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.8.4923-4930.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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