Dissecting The Helicobacter Pylori-Regulated Transcriptome Of B Cells

Persistent infections with the bacterial group-I carcinogen Helicobacter pylori (H. pylori) have been associated with a broad range of gastric disorders, including gastritis, ulceration, gastric cancer or mucosa-associated lymphoid tissue (MALT) lymphoma. Pathogenesis of H. pylori requires a balance between immune tolerance and defense. Although H. pylori induces inflammatory responses, the immune system cannot eliminate the pathogen. The detailed molecular mechanisms of how H. pylori interferes with cells of the immune system, in particular infiltrated B cells, are not well investigated. Previously, it was shown that the bacterial effector and oncoprotein cytotoxin-associated gene A (CagA) is delivered into B cells followed by its tyrosine-phosphorylation. To investigate the functional consequences in B cells colonized by CagA-positive H. pylori, we analyzed the global transcriptome of H. pylori-infected Mec-1 cells by RNA sequencing. We found 889 differentially expressed genes (DEGs) and validated JUN, FOSL2, HSPA1B, SRC, CXCR3, TLR-4, TNF-alpha, CXCL8, CCL2, CCL4, MHC class I and MHC class II molecules by qPCR, western blot, flow cytometry and ELISA assays. The H. pylori-specific mRNA expression signature reveals a downregulation of inflammation- and migration-associated genes, whereas central signal transduction regulators of cell survival and death are upregulated.