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Infection and Immunity, March 2003, p. 1161-1169, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1161-1169.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Rho GTPase Is Activated by Cytotoxic Necrotizing Factor 1 in Peripheral Blood T Lymphocytes: Potential Cytotoxicity for Intestinal Epithelial Cells

Patrick Brest,¹ Baharia Mograbi,¹ Véronique Hofman,² Agnès Loubat,¹ Bernard Rossi,¹ Patrick Auberger,³ and Paul Hofman^1,2*

INSERM 364,¹ Laboratoire d'Anatomie-Pathologique,² INSERM 526, Faculté de Médecine, 06107 Nice Cédex 02, France³

Received 7 August 2002/ Returned for modification 8 October 2002/ Accepted 23 November 2002

Some strains of Escherichia coli related to acute cystitis or colitis produce a toxin named cytotoxic necrotizing factor 1 (CNF-1). CNF-1 mediates its effects on epithelial cells or phagocytes via the permanent activation of small GTP-binding proteins, caused by the toxin-induced deamidation of Glu⁶³ of p21 Rho. The behavior of peripheral blood T lymphocytes during the acute phase of bacterial colitis has been poorly investigated. Our study was conducted to test whether (i) peripheral blood T lymphocytes can be activated by CNF-1 and (ii) CNF-1-activated T lymphocytes are cytotoxic against intestinal epithelial cells. Activation of T lymphocytes by CNF-1 was assessed by electrophoresis, flow cytometry, confocal microscopy, and electron microscopy studies. Assays for migration and adherence of CNF-1-treated T lymphocytes were performed in Transwell chambers with T84 intestinal epithelial cells grown on polycarbonate semipermeable filters. CNF-1 induced a decrease in the electrophoretic mobility of the GTP-binding protein Rho in treated T lymphocytes. CNF-1 provoked an increase in the content of actin stress fibers and pseudopodia in T lymphocytes. Several adherence molecules were clustered into cytoplasmic projections in CNF-1-treated T lymphocytes and adherence of such lymphocytes on the basolateral pole of T84 was increased, resulting in cytotoxicity toward epithelial cells. Such enhanced adherence in response to CNF-1 was dependent on p42-44^MAP kinase activation of T lymphocytes. Taken together, these results suggest that CNF-1, by acting on T lymphocytes, may increase in an important fashion the virulence of certain strains of E. coli against the intestinal epithelia.

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* Corresponding author. Mailing address: INSERM Unité 364, IFR 50, Faculté de Médecine, avenue de Valombrose, 06107 Nice, Cédex 02, France. Phone: 33 4 93 37 77 59. Fax: 33 4 93 81 94 56. E-mail: hofman{at}unice.fr.

Editor: J. D. Clements

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Infection and Immunity, March 2003, p. 1161-1169, Vol. 71, No. 3
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.3.1161-1169.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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