Expression of IRF8 in gastric epithelial cells confers protective innate immunity against Helicobacter pylori infection

摘要

Interferon regulatory factor 8 (IRF8) is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. However, the role of IRF8 in nonhematopoietic systems remains poorly understood. In this study, we provide evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting H. pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which in turn promoted IFN-γ expression by gastric epithelial cells (GECs). Mice deficient of IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-γ. Genome-wide analyses of IFN-γ-treated GECs by ChIP-seq and RNA-seq led to the identification of IRF8 target genes, with many belonging to the IFN regulated gene family that was previously observed in immune cells. Our results identify the IRF8-IFN-γ circuit as a novel gastric innate immune mechanism in host defense against infection of H. pylori.