Interferon γ-Signature Transcript Profiling and IL-23 Upregulation in Response toHelicobacter PyloriInfection

Abstract

Helicobacter pylori infection is the major cause of gastroduodenal pathologies including gastric cancer. The long persistence of bacteria and the type of immune and inflammatory response determine the clinical issue. In this study, the global gene expression profile after 6 and 12 months of H. pylori infection was investigated in the mouse stomach, using the Affymetrix GeneChip Mouse Expression Array A430. Genes related to the inflammatory and immune responses were focused. Levels of selected transcripts were confirmed by reverse transcription polymerase chain reaction. Twenty-five and nineteen percent of the differentially expressed genes observed at 6 and 12 months post-infection respectively, were related to immune response. They are characterized by an interferon (lFN)y-dependent expression associated to a T helper 1 (Thl) polarised response. In-depth analysis revealed that an up-regulation of IL-23pI9, took place in the stomach of H. pylori infected-mice. Strong IL-23p19 levels were also confirmed in gastric biopsies from H. pylori-infected patients with chronic gastritis, as compared to healthy subjects. Our microarray analysis revealed also, a high decrease of H+K+-ATPase transcripts in the presence of the H. pylori infection. Association of gastric Thl immune response with hypochlorhydria through the down-regulation of H+K+-ATPase contributes to the genesis of lesions upon the H. pylori infection. Our data highlight that the up-regulation of IL-23 and of many IFNy signature transcripts occur early on during the host response to H. pylori, and suggest that this type of immune response may promote the severity of the induced gastric lesions. Half of the world population is chronically infected by Helicobacter pylori, a bacterium that specifically colonizes the human stomach. The H. pylori infection is the major cause of gastroduodenal pathologies such as chronic gastritis, peptic ulcer diseases, gastric adenocarcinoma and lymphoma (1). The most important co-factor in the induction of Helicobacter-related disease is the host immune response. Studies in humans and in animal models have shown that a pro-inflammatory T helper (Th) 1 response, with high levels of interferon (IFN)y, interleukin (IL)-12, IL-17 and IL-18, is associated

A Double-Edged Sword: Roles of Helicobacter Pylori in Gastric Carcinoma

“…During H. pylori infection, significant overexpression of MHC II antigen-presenting genes, IL-7R ubiquitin-D, CXCR4, lactoferrin immune response-related genes, CXCL-2 and -13, CCL18 chemokine ligand, and VCAM-1 genes have been established (Galamb et al, 2008). In addition, IL-23p19 up-regulation is confirmed in gastric biopsies from both H. pylori infected-mice and patients with chronic gastritis (Vivas et al, 2008). CCR6 is markedly upregulated in CD3 (+) T cells infiltrating the gastric mucosa and has been reported to mediate lymphocyte homeostasis and immune responses in mucosal tissue Tsai & Hsu, 2010).…”

“…During H. pylori infection, activated macrophages produce IL-18, which stimulates the IFN-secretion by NK and T cells (Kawabata et al, 2001). Nevertheless, Th1 immune response in the stomach may destroy the proliferation / apoptosis balance and promote the severity of H. pylori-induced gastric lesions (Xia et al, 2001;Vivas et al, 2008). In the host, the innate immune response usually represents by TLRs and Nod-like receptors that recognize their specific ligands, activate transcription factors including NF-kB, AP-1 and CREB-1, and induce inflammatory cytokines such as IL-8, IL-12, IL-6, IL-1 , IL-18, TNFand IL-10 (Sánchez-Zauco et al, 2010).…”

Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model: identification of CD177 as a novel prognostic factor in patients with gastric cancer

“…High throughput microarray technology provides a powerful tool for comprehensive gene analysis, already applied to assess gene expression patterns in both human samples and animal models of gastric disorders [7-16]. Although many researchers have focused on gene expression in H. pylori -treated gastric cell lines [17-19], results in cell culture do not necessarily correlate with expression of specific genes in the in vivo microenvironment featuring host immune responses and stromal-epithelial interactions in cancers.…”

Helicobacter PyloriHP0175 Promotes the Production of IL-23, IL-6, IL-1β and TGF-β

“…Interleukin (IL)-1b, IL-6, transforming growth factor-b (TGF-b), and IL-23 are key cytokines in the differentiation and expansion of Th 17 cells (13,14). IL-17, IL-21 and IL-23 are up-regulated in H. pylori-infected gastric mucosa (10,15).…”