Induction of Maturation and Cytokine Release of Human Dendritic Cells byHelicobacter pylori

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Abstract
Helicobacter pyloricauses a persistent infection in the human stomach, which can result in chronic gastritis and peptic ulcer disease. Despite an intensive proinflammatory response, the immune system is not able to clear the organism. However, the immune escape mechanisms of this common bacterium are not well understood. We investigated the interaction betweenH. pyloriand human dendritic cells. Dendritic cells (DCs) are potent antigen-presenting cells and important mediators between the innate and acquired immune system. Stimulation of DCs with different concentrations ofH. pylorifor 8, 24, 48, and 72 h resulted in dose-dependent interleukin-6 (IL-6), IL-8, IL-10 and IL-12 production. Lipopolysaccharide (LPS) fromEscherichia coli, a known DC maturation agent, was used as a positive control. The cytokine release after stimulation with LPS was comparable to that induced byH. pyloriexcept for IL-12. After LPS stimulation IL-12 was only moderately released compared to the large amounts of IL-12 induced byH. pylori. We further investigated the potential ofH. pylorito induce maturation of DCs. Fluorescence-activated cell sorting analysis of cell surface expression of maturation marker molecules such as CD80, CD83, CD86, and HLA-DR revealed equal upregulation after stimulation withH. pylorior LPS. We found no significant differences betweenH. pyloriseropositive and seronegative donors of DCs with regard to cytokine release and upregulation of surface molecules. These data clearly demonstrate thatH. pyloriinduces a strong activation and maturation of human immature DCs.

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