ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation

• Published in: Gut microbes Vol. 16; no. 1; p. 2402543
• Main Authors: Neuper, Theresa, Frauenlob, Tobias, Dang, Hieu-Hoa, Krenn, Peter W., Posselt, Gernot, Regl, Christof, Fortelny, Nikolaus, Schäpertöns, Veronika, Unger, Michael S., Üblagger, Gunda, Neureiter, Daniel, Mühlbacher, Iris, Weitzendorfer, Michael, Singhartinger, Franz, Emmanuel, Klaus, Huber, Christian G., Wessler, Silja, Aberger, Fritz, Horejs-Hoeck, Jutta
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2024; Taylor & Francis Group
• Subjects: Adenosine Diphosphate - metabolism; ADP-heptose; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Gastric Mucosa - immunology; Gastric Mucosa - metabolism; Gastric Mucosa - microbiology; H. pylori; Helicobacter Infections - immunology; Helicobacter Infections - microbiology; Helicobacter pylori - immunology; Heptoses - metabolism; Heptoses - pharmacology; Humans; Immune Evasion; Lipopolysaccharides; Research Paper; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; TLR2; Toll-Like Receptor 2 - metabolism; type I IFN; H. pylori; Dendritic cells; type I IFN; ADP-heptose; TLR2
• ISSN: 1949-0976; 1949-0984; 1949-0984
• DOI: 10.1080/19490976.2024.2402543

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.