ADP-heptose attenuates <i>Helicobacter pylori</i> -induced dendritic cell activation

Sophisticated immune evasion strategies enable <i>Helicobacter pylori (H. pylori)</i> 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 <i>H. pylori</i> and host immunity, spatial profiling was used to monitor immune cells in <i>H. pylori</i> 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 <i>H. pylori</i>-induced DC maturation and subsequent T cell responses. Mechanistically, we report that <i>H. pylori</i> uptake and subsequent DC activation by an ADP-heptose deficient <i>H. pylori</i> strain depends on TLR2. Moreover, ADP-heptose attenuates full-fledged activation of primary human DCs in the context of <i>H. pylori</i> infection by impairing type I IFN signaling. This study reveals that ADP-heptose mitigates host immunity during <i>H. pylori</i> infection.