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Clin Exp Immunol. 2011 Oct;166(1):34-45. doi: 10.1111/j.1365-2249.2011.04447.x.

Stimulation of dendritic cells with Helicobacter pylori vacuolating cytotoxin negatively regulates their maturation via the restoration of E2F1.

Author information

  • 1Department of Microbiology, Hanyang University College of Medicine Department of Internal Medicine, Seoul National University College of Medicin Department of Food and Nutrition, Yonsei University, Seoul Department of Biotechnology, Joongbu University, Choongnam, Korea. jungmogg@hanyang.ac.kr

Abstract

Helicobacter pylori induces an infiltration of dendritic cells (DCs) into the infected gastric mucosa. Although DCs play an important role in the regulation of inflammation, the effects of H. pylori vacuolating cytotoxin (VacA) on DC maturation process have not yet been elucidated. The role of VacA in DC maturation following co-exposure to Escherichia coli lipopolysaccharide (LPS) was investigated. The treatment of immature DCs with LPS up-regulated the expression of surface molecules [e.g. CD40, CD80, CD86 and major histocompatibility complex (MHC) class II], as well as the production of cytokines [e.g. interleukin (IL)-1β, IL-12p70 and tumour necrosis gactor (TNF)-α] compared with those of unstimulated controls. Co-stimulation with H. pylori VacA significantly reduced the up-regulated DC maturation markers induced by LPS. In addition, VacA sustained the immature state of DCs with high endocytosis and low migratory capacity. The LPS-induced down-regulation of E2F1 expression in DCs was recovered by co-stimulation with VacA. Moreover, suppression of E2F1 by small interfering RNA resulted in a significant recovery of the inhibited DC maturation by VacA. In contrast, VacA did not affect nuclear factor (NF)-κB responses to LPS and the NF-κB signal was not associated with VacA-induced inhibition of DC maturation. These results suggest that the exposure of DCs to H. pylori VacA negatively regulates DC maturation via the restoration of E2F1. The immunomodulatory action of VacA on DCs may contribute to the ability of VacA-producing H. pylori to establish a persistent infection in the gastric mucosa.

© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

PMID:
21910723
[PubMed - indexed for MEDLINE]
PMCID:
PMC3193917
Free PMC Article

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