This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deml, L. Articles by Schneider-Brachert, W. Search for Related Content PubMed PubMed Citation Articles by Deml, L. Articles by Schneider-Brachert, W.

Characterization of the Helicobacter pylori Cysteine-Rich Protein A as a T-Helper Cell Type 1 Polarizing Agent

Ludwig Deml,¹ Michael Aigner,¹ Jochen Decker,^1, Alexander Eckhardt,¹ Christian Schütz,¹ Peer R. E. Mittl,² Sascha Barabas,¹ Stefanie Denk,¹ Gertrud Knoll,¹ Norbert Lehn,¹ and Wulf Schneider-Brachert^1*

Institute for Medical Microbiology and Hygiene, University of Regensburg, D-93053 Regensburg, Germany,¹ Biochemisches Institut, Universität Zürich, CH-8057 Zürich, Switzerland²

Received 29 October 2004/ Returned for modification 2 December 2004/ Accepted 9 March 2005

Predominant T-helper 1 (Th1) responses with increased gamma interferon (IFN-) levels have been proposed to play an important role in Helicobacter pylori-induced gastritis and peptic ulceration. However, bacterial factors contributing to the initiation of Th1 polarization of H. pylori-specific immune responses have not been characterized in detail thus far. We report here on the identification of Helicobacter cysteine-rich protein A (HcpA) as a novel proinflammatory and Th1-promoting protein. The capacity of HcpA to induce immune activation was studied in splenocyte cultures of naive H. pylori-negative mice. HcpA stimulated the release of high concentrations of the proinflammatory and Th1-promoting cytokines interleukin-6 (IL-6) and IFN-, in addition to significant levels of IL-12, tumor necrosis factor alpha, and IL-10. The observed cytokine profile was comparable to that induced by lipopolysaccharide but differed in the kinetics and maximum levels of cytokine production. In addition, HcpA-induced cytokine release resembled that observed upon incubation with H. pylori except for IL-10, which was only moderately released upon HcpA stimulation. Both HcpA- and H. pylori-mediated IFN- production was drastically reduced by a neutralizing antibody against IL-12 but not by an anti-IL-2 antibody. Thus, HcpA seems to represent a novel bacterial virulence factor triggering the release of a concerted set of cytokines to instruct the adaptive immune system for the initiation of proinflammatory and Th1-biased immunity.

Editor: J. B. Bliska

Present address: Accenture GmbH München, D-80539 Munich, Germany.

This article has been cited by other articles:

• Giannakis, M., Chen, S. L., Karam, S. M., Engstrand, L., Gordon, J. I. (2008). Helicobacter pylori evolution during progression from chronic atrophic gastritis to gastric cancer and its impact on gastric stem cells. Proc. Natl. Acad. Sci. USA 105: 4358-4363 [Abstract] [Full Text]  
• Algood, H. M. S., Cover, T. L. (2006). Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses. Clin. Microbiol. Rev. 19: 597-613 [Abstract] [Full Text]