title: Characterization of the Helicobacter pylori cysteine-rich protein A as a T-helper cell type 1 polarizing agent.
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, 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-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.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Deml
authors.forename: Michael
authors.initials: M
authors.lastname: Aigner
authors.forename: Jochen
authors.initials: J
authors.lastname: Decker
authors.forename: Alexander
authors.initials: A
authors.lastname: Eckhardt
authors.forename: Christian
authors.initials: C
authors.lastname: Schütz
authors.forename: Peer R E
authors.initials: PR
authors.lastname: Mittl
authors.forename: Sascha
authors.initials: S
authors.lastname: Barabas
authors.forename: Stefanie
authors.initials: S
authors.lastname: Denk
authors.forename: Gertrud
authors.initials: G
authors.lastname: Knoll
authors.forename: Norbert
authors.initials: N
authors.lastname: Lehn
authors.forename: Wulf
authors.initials: W
authors.lastname: Schneider-Brachert
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000276:immunology* / Q000494:pharmacology; D001618:beta-Lactamases / Q000276:immunology* / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D037521:Virulence Factors; D018664:Interleukin-12; D007371:Interferon-gamma; C410728:hcpA protein, Helicobacter pylori; D001618:beta-Lactamases