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Infect. Immun. doi:10.1128/IAI.01935-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Inhibitory effect of enterohepatic Helicobacter hepaticus on innate immune responses of mouse intestinal epithelial cells

Torsten Sterzenbach, Sae Kyung Lee, Birgit Brenneke, Franz von Goetz, David B. Schauer, James G. Fox, Sebastian Suerbaum*, and Christine Josenhans*

Hannover Medical School, Institute for Medical Microbiology and Hospital Epidemiology, 30625 Hannover, Germany; MIT, Division of Comparative Medicine, Cambridge, Massachusetts, U.S.A.; MIT, Division of Biological Engineering, Cambridge, Massachusetts, U.S.A.

* To whom correspondence should be addressed. Email: suerbaum.sebastian{at}mh-hannover.de. josenhans.christine{at}mh-hannover.de.


   Abstract

Enterohepatic Helicobacter species infect the intestinal tract and biliary tree of various mammals, including mouse and human, 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 allows for the functional analysis of bacterial factors that may play a role in these diseases. We tested the hypothesis that H. hepaticus may suppress or evade innate immune responses of mouse intestinal epithelial cells, thus allowing this pathogen to induce or contribute to chronic inflammatory disease. We demonstrate in the present study that 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 lipopolysaccharide (LPS) were able to antagonize TLR4- and TLR5-mediated immune responses of intestinal epithelial cells. H. hepaticus lysate and LPS inhibited development of endotoxin tolerance towards E. coli LPS. Suppression of innate immune responses by H. hepaticus LPS thus may affect intestinal responses to resident microbial flora, epithelial homeostasis, and intestinal inflammatory conditions.




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