Supporting data for "ADP-heptose attenuates Helicobacter pylori-induced dendritic cell activation"

Description

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 investi-
gated 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.