Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage.

Abstract

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphomas. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Enhanced gastric epithelial cell apoptosis during H. pylori infection was suggested to play an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition to directly triggering apoptosis, H. pylori induces sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells. Human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death-receptor signaling. The induction of TRAIL sensitivity by H. pylori is dependent upon the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex through downregulation of cellular FLICE-inhibitory protein. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, significant increases in CCR6+ CD3+ T cell infiltration in the gastric mucosa was observed, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These mechanisms initiate chemokine-mediated T lymphocyte trafficking into inflamed epithelium and induce mucosal injury during Helicobacter infection. This article will review recent findings on the interactions of H. pylori with host-epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation and mucosal damage.

• Authors: Hwei-Fang Tsai, Ping-Ning Hsu
• Journal: Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi (J Microbiol Immunol Infect) Vol. 50 Issue 1 Pg. 4-9 (Feb 2017) ISSN: 1995-9133 [Electronic] England
• PMID: 26947589 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2016. Published by Elsevier B.V.

Chemical References

• Chemokines
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• CASP8 protein, human
• Caspase 8

Topics

• Apoptosis
• Caspase 8 (metabolism)
• Chemokines (metabolism)
• Gastric Mucosa (pathology)
• Helicobacter Infections (pathology)
• Helicobacter pylori (pathogenicity)
• Host-Pathogen Interactions
• Humans
• Inflammation (pathology)
• Signal Transduction
• T-Lymphocytes (immunology)
• TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Transcriptional Activation