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Review
. 2010 Jul;7(4):255-9.
doi: 10.1038/cmi.2010.2. Epub 2010 Mar 1.

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

Affiliations
Review

Interplay between Helicobacter pylori and immune cells in immune pathogenesis of gastric inflammation and mucosal pathology

Hwei-Fang Tsai et al. Cell Mol Immunol. 2010 Jul.

Abstract

Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, leading to chronic gastritis, peptic ulcers, gastric carcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Recent studies have shown that apoptosis of gastric epithelial cells is increased during H. pylori infection. Apoptosis induced by microbial infections are factors implicated in the pathogenesis of H. pylori infection. The enhanced gastric epithelial cell apoptosis in H. pylori infection has been 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 (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells via modulation of TRAIL apoptosis signaling. Moreover, H. pylori infection induces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. pylori infection, there was significantly increased CCR6(+)CD3(+ )T-cell infiltration in the gastric mucosa, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These results implicate that the interaction between CCL20 and CCR6 may play a role in recruiting T cells to the sites of inflammation in the gastric mucosa during Helicobacter infection. Through these mechanisms, chemokine-mediated T lymphocyte trafficking into inflamed epithelium is initiated and the mucosal injury in Helicobacter infection is induced. This article will review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation, mucosal damage and development of MALT lymphomas.

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Figures

Figure 1
Figure 1
Immune pathogenesis of gastric mucosa damage in H. pylori infection. In the absence of H. pylori infection, there are very few T cells infiltrating into the gastric mucosa, which do not induce apoptosis in gastric epithelial cells. In contrast, in the presence of H. pylori infection, H. pylori induce inflammation and production of chemokine CCL20 to recruit CCR6 expressing activated CD4+ T cells infiltrated to the sites of inflammation in the gastric mucosa. The TRAIL expressing T cells subsequently induce apoptosis in the H. pylori-infected gastric epithelia cells. Meanwhile, immune cells constituting MALTs migrate to and infiltrate the site of H. pylori infection in the gastric mucosa, and in such circumstances, CagA may be injected into lymphocytes as well as gastric epithelial cells. When CagA is transloacted into B lymphocytes, it may induce activation of B lymphocytes to proliferate. The molecular mechanism of H. pylori-induced susceptibility to TRAIL-mediated apoptosis in gastric epithelia cells is shown in the lower inlet of the figure. In the absence of H. pylori infection, TRAIL engagement with death receptors on gastric epithelial cells induces only weak activation of caspase 8, and is not able to activate the caspase 8 downstream signals to trigger cell death. In contrast, in the presence of H. pylori infection, H. pylori enhance the assembly of TRAIL death-inducing signaling complex (DISC) after TRAIL engagement, to augment the activation of caspase 8 and to convey the death signal to mitochondria via cleavage of Bid, leading to activation of mitochondrial pathway and breaking the apoptosis resistance. CagA, cytotoxin-associated gene A; FADD, Fas-associated protein with death domain; MALT, mucosa-associated lymphoid tissue; TRAIL, tumor-necrosis factor-related apoptosis-inducing ligand.

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