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Infection and Immunity, July 2003, p. 4052-4058, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4052-4058.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Salmonella enterica Serovar Typhimurium Translocated Leucine-Rich Repeat Effector Protein Inhibits NF-{kappa}B-Dependent Gene Expression

Andrea Haraga1 and Samuel I. Miller1,2,3*

Departments of Microbiology,1 Medicine,2 Genome Sciences, University of Washington, Seattle, Washington 98195-77103

Received 17 October 2002/ Returned for modification 28 January 2003/ Accepted 26 March 2003

Nontyphoidal salmonellae are enteric pathogens that cause acute gastroenteritis and colonize the intestinal tract for prolonged periods. In the intestinal epithelia, these bacteria induce secretion of proinflammatory cytokines, such as interleukin-8 (IL-8), which leads to a profound inflammatory response through recruitment of polymorphonuclear leukocytes. Production of IL-8 induced by Salmonella spp. is due to the activation of the transcription factors nuclear factor {kappa}B (NF-{kappa}B) and activator protein-1 (AP-1). This work demonstrates that Salmonella enterica serovar Typhimurium can downmodulate IL-8 production after invasion of intestinal epithelial cells. The Salmonella translocated effector proteins SspH1 and SptP participate in this process. SspH1 is a member of the bacterial LPX repeat protein family that localizes to the mammalian nucleus and inhibits NF-{kappa}B-dependent gene expression. A Shigella flexneri translocated effector, IpaH9.8, which has a similar structure and subcellular localization in mammalian cells, also inhibits NF-{kappa}B-dependent gene expression. We propose that suppression of inflammatory responses by intracellular S. enterica serovar Typhimurium, and perhaps Shigella flexneri, contributes to bacterial colonization of host tissues and pathogenesis.

* Corresponding author. Mailing address: Department of Medicine, University of Washington, Health Sciences Building, K-140, Box 357710, Seattle, WA 98195-7710. Phone: (206) 616-5107. Fax: (206) 616-4295. E-mail: millersi{at}u.washington.edu.

Editor: V. J. DiRita

Infection and Immunity, July 2003, p. 4052-4058, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.4052-4058.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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