Mechanisms of interacting <i>Helicobacter pylori</i> with gastric mucosal epithelium. II. A reaction of gastric epithelium on <i>Helicobacter pylori</i> colonization and persistence

Abstract

Gastric and duodenal recurrent inflammatory diseases have a high prevalence, but the role played by microbes in its development remained unclear. However, the data published in 1983 by Marshall and Warren about isolating Helicobacter pylori from the stomach mucosa of the patient with gastritis and proposing relevant cultivation methods was the turning point in investigating etiology of the upper digestive tract inflammatory disorders. Moreover, it was shown that the majority of H. pylori spp. are found within the gastric lumen upon colonization, whereas around 20% of them are attached to the epithelial cells in the stomach. In addition, effects of interacting H. pylori with gastric epithelium and activation of some defense mechanisms due to bacterial colonization and spreading were analyzed. It was found that along with triggering pro-inflammatory response induced by proteins VacA as well as phosphorylated/unphosphorylated CagA, wherein the latter is able to induce a set of protective reactions H. pylori disrupts intercellular contacts, affects epithelial cell polarity and proliferation, and activates SHP-2 phosphatase resulting in emerging diverse types of cellular responses. The activation mechanisms for the mitogen-activated protein kinase (MAPK) pathway were discussed. The ability of H. pylori to regulate apoptosis, particularly via its suppression, by expressing ERK kinase and protein MCL1 facilitating bacterial survival in the gastric mucosa as well as beneficial effects related to bacterial circulation on gastric epithelial cell survival elicited by anti-apoptotic factors were also examined. Of note, persistence of H. pylori are mainly determined by activating transcriptional factors including NF-B, NFAT, SRF, T-cell lymphoid enhancing factor (TCF/LEF), regulating activity of MCL1 protein, in turn, being one of the main anti-apoptotic factors, as well as induced production of the migration inhibitory factor (MIF). The role of VacA cytotoxin in triggering epithelial cell apoptosis via caspase-mediated pathways was also considered. Infection with H. pylori is accompanied by release of proinflammatory cytokine cocktail detected both in vitro and in vivo. In particular, bacterial urease activating transcriptional factor NF-B was shown to play a crucial role in inducing cytokine production. Moreover, such signaling pathways may be activated after H. pylori is attached to the cognate receptor in the gastric epithelial surface by interacting with CD74 and MHC class II molecules. Finally, a role for various CD4+ T cell subsets, particularly type 17 T helper cells (Th17) in inducing immune response against H. pylori antigens in gastric mucosa was revealed were also discussed.