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Infection and Immunity, June 2007, p. 2717-2728, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01935-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inhibitory Effect of Enterohepatic Helicobacter hepaticus on Innate Immune Responses of Mouse Intestinal Epithelial Cells{triangledown}

Torsten Sterzenbach,1 Sae Kyung Lee,1,4 Birgit Brenneke,1 Franz von Goetz,1 David B. Schauer,3 James G. Fox,2,3 Sebastian Suerbaum,1* and Christine Josenhans1*

Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, 30625 Hannover, Germany,1 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts,2 Division of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts,3 Institute for Hygiene and Microbiology, University of Wuerzburg, 97070 Wuerzburg, Germany4

Received 7 December 2006/ Returned for modification 2 February 2007/ Accepted 12 March 2007

Enterohepatic Helicobacter species infect the intestinal tracts and biliary trees of various mammals, including mice and humans, and are associated with chronic inflammatory diseases of the intestine, gallstone formation, and malignant transformation. The recent analysis of the whole genome sequence of the mouse enterohepatic species Helicobacter hepaticus allowed us to perform a functional analysis of bacterial factors that may play a role in these diseases. We tested the hypothesis that H. hepaticus suppresses or evades innate immune responses of mouse intestinal epithelial cells, which allows this pathogen to induce or contribute to chronic inflammatory disease. We demonstrated in the present study that the innate immune responses of intestinal epithelial cells to lipopolysaccharide (LPS) via Toll-like receptor 4 (TLR4) and to flagellin-mediated activation via TLR5 are reduced by H. hepaticus infection through soluble bacterial factors. In particular, H. hepaticus lysate and the soluble component LPS antagonized TLR4- and TLR5-mediated immune responses of intestinal epithelial cells. H. hepaticus lysate and LPS inhibited development of endotoxin tolerance to Escherichia coli LPS. Suppression of innate immune responses by H. hepaticus LPS thus may affect intestinal responses to the resident microbial flora, epithelial homeostasis, and intestinal inflammatory conditions.


* Corresponding author. Mailing address: Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, 30625 Hannover, Germany. Phone for Sebastian Suerbaum: 495115326769. Fax: 495115324366. E-mail: suerbaum.sebastian{at}mh-hannover.de. Phone for Christine Josenhans: 495115324348. Fax: 495115324355. E-mail: josenhans.christine{at}mh-hannover.de

{triangledown} Published ahead of print on 19 March 2007.

Editor: F. C. Fang


Infection and Immunity, June 2007, p. 2717-2728, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01935-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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