Abstract

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 , * 1 Institute for Medical Microbiology and Hygiene, University of Regensburg, D-93053 Regensburg, Germany 2 Biochemisches Institut, Universität Zürich, CH-8057 Zürich, Switzerland ABSTRACT Predominant T-helper 1 (Th1) responses with increased gamma interferon (IFN-γ) 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-γ, 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-γ 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.