Analysis of metagenome collected from H. pylori-infected mouse stomach

Helicobacter pylori (H. pylori) causes assorted gastrointestinal disorders. H. pylori-specific T cells develop during infection, which is prerequisite for the induction of gastritis and malignancy. How the innate immune system senses H. pylori to prime T cells remains unclear. We report that cholesteryl glucosides in H. pylori activate innate immunity through C-type lectin receptors (CLRs). Cholesteryl acyl a-glucoside (aCAG) was identified as a ligand for Mincle (Clec4e). Upon H. pylori infection, T cell responses and gastritis were ameliorated in Mincle-deficient mice, although bacterial numbers were comparable. Thus, the cholesteryl lipid-CLR axis exacerbates H. pylori-induced gastric inflammation with limited contribution to protective immunity.