Helicobacter pylori CagA: From Pathogenic Mechanisms to Its Use as an Anti-Cancer Vaccine
Open Access
- 1 January 2013
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 4, 328
- https://doi.org/10.3389/fimmu.2013.00328
Abstract
Helicobacter pylori colonizes the gastric mucosa of more than 50% of the human population, causing chronic inflammation, which however is largely asymptomatic. Nevertheless, H. pylori-infected subjects can develop chronic gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. Chronic exposure to the pathogen and its ability to induce epithelial-to-mesenchymal transition (EMT) through the injection of CagA into gastric epithelial cells may be key triggers of carcinogenesis. By deregulating cell-cell and cell-matrix interactions as well as DNA methylation, histone modifications, expression of micro RNAs, and resistance to apoptosis, EMT can actively contribute to early stages of the cancer formation. Host response to the infection significantly contributes to disease development and the concomitance of particular genotypes of both pathogen and host may turn into the most severe outcomes. T regulatory cells (Treg) have been recently demonstrated to play an important role in H. pylori-related disease development and at the same time the Treg-induced tolerance has been proposed as a possible mechanism that leads to less severe disease. Efficacy of antibiotic therapies of H. pylori infection has significantly dropped. Unfortunately, no vaccine against H. pylori is currently licensed, and protective immunity mechanisms against H. pylori are only partially understood. In spite of promising results obtained in animal models of infection with a number of vaccine candidates, few clinical trials have been conducted so far and with no satisfactory outcomes. However, prophylactic vaccination may be the only means to efficiently prevent H. pylori-associated cancers.This publication has 98 references indexed in Scilit:
- Chromatin Modifications and Their FunctionCell, 2007
- The Epigenomics of CancerCell, 2007
- A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodellingNature, 2006
- Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylationGut, 2006
- Helicobacter pylori-Specific CD4+T Cells Home to and Accumulate in the HumanHelicobacter pylori-Infected Gastric MucosaInfection and Immunity, 2005
- Helicobacter pyloristimulates hostvascular endothelial growth factor‐A(vegf‐A) gene expression via MEK/ERK‐dependent activation of Sp1 and Sp3The FASEB Journal, 2003
- The Helicobacter pylori CagA protein induces cortactin dephosphorylation and actin rearrangement by c-Src inactivationThe EMBO Journal, 2003
- DNA methylation patterns and epigenetic memoryGenes & Development, 2002
- Role of hsp70 in cytokine productionCellular and Molecular Life Sciences, 1994
- Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pyloriThe Lancet, 1993