ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation

Theresa Neuper, Tobias Frauenlob, Hieu-Hoa Dang, Peter W Krenn, Gernot Posselt, Christof Regl, Nikolaus Fortelny, Veronika Schäpertöns, Michael S Unger, Gunda Üblagger, Daniel Neureiter, Iris Mühlbacher, Michael Weitzendorfer, Franz Singhartinger, Klaus Emmanuel, Christian G Huber, Silja Wessler, Fritz Aberger, Jutta Horejs-Hoeck

Research output: Contribution to journalArticlepeer-review

Abstract

Sophisticated immune evasion strategies enable Helicobacter pylori (H. pylori) to colonize the gastric mucosa of approximately half of the world's population. Persistent infection and the resulting chronic inflammation are a major cause of gastric cancer. To understand the intricate interplay between H. pylori and host immunity, spatial profiling was used to monitor immune cells in H. pylori infected gastric tissue. Dendritic cell (DC) and T cell phenotypes were further investigated in gastric organoid/immune cell co-cultures and mechanistic insights were acquired by proteomics of human DCs. Here, we show that ADP-heptose, a bacterial metabolite originally reported to act as a bona fide PAMP, reduces H. pylori-induced DC maturation and subsequent T cell responses. Mechanistically, we report that H. pylori uptake and subsequent DC activation by an ADP-heptose deficient H. pylori strain depends on TLR2. Moreover, ADP-heptose attenuates full-fledged activation of primary human DCs in the context of H. pylori infection by impairing type I IFN signaling. This study reveals that ADP-heptose mitigates host immunity during H. pylori infection.

Original languageEnglish
Pages (from-to)2402543
JournalGut Microbes
Volume16
Issue number1
DOIs
Publication statusPublished - 17 Sept 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

Keywords

  • Helicobacter pylori/immunology
  • Dendritic Cells/immunology
  • Humans
  • Helicobacter Infections/microbiology
  • Toll-Like Receptor 2/metabolism
  • Immune Evasion
  • Heptoses/metabolism
  • Gastric Mucosa/microbiology
  • T-Lymphocytes/immunology
  • Adenosine Diphosphate/metabolism
  • Lipopolysaccharides

Fields of Science and Technology Classification 2012

  • 106 Biology

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