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Infection and Immunity, July 2004, p. 3849-3854, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3849-3854.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Intestinal P Glycoprotein Acts as a Natural Defense Mechanism against Listeria monocytogenes

Brien L. Neudeck,^1* Jennifer M. Loeb,¹ Nancy G. Faith,² and Charles J. Czuprynski²

The University of Wisconsin School of Pharmacy,¹ The University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin²

Received 13 November 2003/ Returned for modification 18 December 2003/ Accepted 22 March 2004

Mechanisms by which the intestinal epithelium resists invasion by food-borne pathogens such as Listeria monocytogenes are an evolving area of research. Intestinal P glycoprotein is well known to limit the absorption of xenobiotics and is believed to act as a cytotoxic defense mechanism. The aim of this study was to determine if intestinal P glycoprotein is involved in host defense against L. monocytogenes. Caco-2 cells and a P-glycoprotein-overexpressing subclone (Caco-2/MDR) were employed in addition to mdr1a^–/– mice and wild-type controls. In vitro invasion assays and in vivo experiments were employed to measure bacterial invasion and dissemination. In addition, L. monocytogenes proteins were labeled with [³⁵S]methionine, and the transepithelial transport across Caco-2 monolayers was characterized in both directions. Overexpression of P glycoprotein in Caco-2/MDR cells led to increased resistance to L. monocytogenes invasion, whereas P-glycoprotein inhibition led to increased invasion. Flux of [³⁵S]methionine-labeled L. monocytogenes proteins was significantly greater in the basolateral-to-apical direction than in the apical-to-basolateral direction, indicating dependence on an apically located efflux transporter. Moreover, inhibiting P glycoprotein reduced the basolateral-to-apical flux of the proteins. Early dissemination of L. monocytogenes from the gastrointestinal tract was significantly greater in the mdr1a^–/– mice than in wild-type controls. Expression and function of intestinal P glycoprotein is an important determinant in resistance to early invasion of L. monocytogenes.

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* Corresponding author. Mailing address: University of Wisconsin School of Pharmacy, 777 Highland Ave., Madison, WI 53705-2222. Phone: (608) 265-1168. Fax: (608) 265-5421. E-mail: blneudeck{at}pharmacy.wisc.edu.

Editor: J. B. Bliska

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Infection and Immunity, July 2004, p. 3849-3854, Vol. 72, No. 7
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.7.3849-3854.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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