Helicobacter pylori (H. pylori) colonizes the gastric mucosa of approximately 50% of the world’s population. While it is well established that H. pylori is a major cause of gastric cancer, it has only recently been reported that H. pylori can also have adverse effects on immunological processes, including autoimmune diseases and immunotherapies. Understanding the paradoxical interplay between H. pylori and the human immune system will therefore be beneficial to improve a variety of therapeutic approaches. Here we show that ADP-heptose, a metabolite originally reported to act as a bona fide PAMP, attenuates full-fledged activation of primary human dendritic cells in the context of H. pylori infection by impairing type I IFN signaling, which in turn results in reduced DC maturation and T cell activation. Thus, this study provides novel mechanistic insights into how H. pylori utilizes ADP-heptose to mitigate host immunity.