ADP-heptose attenuates -induced dendritic cell activation.

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