Characterization of the Helicobacter pylori cysteine-rich protein A as a T-helper cell type 1 polarizing agent

Deml, Ludwig and Aigner, Michael and Decker, Jochen and Eckhardt, Alexander and Schuetz, Christian and Mittl, Peer R. E. and Barabas, Sascha and Denk, Stefanie and Knoll, Gertrud and Lehn, Norbert and Schneider-Brachert, Wulf (2005) Characterization of the Helicobacter pylori cysteine-rich protein A as a T-helper cell type 1 polarizing agent. INFECTION AND IMMUNITY, 73 (8). pp. 4732-4742. ISSN 0019-9567, 1098-5522

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Abstract

Predominant T-helper 1 (Th1) responses with increased gamma interferon (IFN-gamma) 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-gamma, 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, HepA-induced cytokine release resembled that observed upon incubation with H. pylori except for IL-10, which was only moderately released upon HcpA stimulation. Both HepA- and H. pylori-mediated IFN-gamma 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.

Item Type: Article
Uncontrolled Keywords: HUMAN DENDRITIC CELLS; GASTRIC EPITHELIAL-CELLS; PEPTIC-ULCER DISEASE; GAMMA-INTERFERON; INTERLEUKIN-8 PRODUCTION; VIRULENCE FACTORS; IN-VITRO; INFECTION; EXPRESSION; PATHOGENESIS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 May 2021 07:01
Last Modified: 03 May 2021 07:01
URI: https://pred.uni-regensburg.de/id/eprint/35807

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