ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation

Autor: 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
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Gut Microbes, Vol 16, Iss 1 (2024)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2024.2402543
Popis: 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.
Databáze: Directory of Open Access Journals