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The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms
Open accessAbstract
Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and loosening of tight junctions. Here we report that VacA also interferes with T cell activation by two different mechanisms. Formation of anion-specific channels by VacA prevents calcium influx from the extracellular milieu. The transcription factor NF-AT thus fails to translocate to the nucleus and activate key cytokine genes. A second, channel-independent mechanism involves activation of intracellular signaling through the mitogen-activated protein kinases MKK3/6 and p38 and the Rac-specific nucleotide exchange factor, Vav. As a consequence of aberrant Rac activation, disordered actin polymerization is stimulated. The resulting defects in T cell activation may help H. pylori to prevent an effective immune response leading to chronic colonization of its gastric niche.
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Cites
Cyclooxygenases: Structural, cellular, and molecular biology
Smith, W. L., DeWitt, D. L., & Garavito, R. M. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.145 · Cited by 2,925
Cited by
Pathogenesis of Helicobacter pylori Infection
Kusters, J. G., van Vliet, A. H. M., & Kuipers, E. J. (2006) · Clinical Microbiology Reviews · doi:10.1128/cmr.00054-05 · Cited by 2,526
Helicobacter pylori and Gastric Cancer: Factors That Modulate Disease Risk
Wroblewski, L. E., Peek, R. M., & Wilson, K. T. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00011-10 · Cited by 1,442
Mechanisms of disease: Helicobacter pylori virulence factors
Yamaoka, Y. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.154 · Cited by 666
Persistent bacterial infections: the interface of the pathogen and the host immune system
Monack, D. M., Mueller, A., & Falkow, S. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro955 · Cited by 572
THE PATHOGENESIS OF HELICOBACTER PYLORI–INDUCED GASTRO-DUODENAL DISEASES
Atherton, J. C. (2006) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100125 · Cited by 567
Metadata
- Authors
- Boncristiano, M., Paccani, S. R., Barone, S., Ulivieri, C., Patrussi, L., Ilver, D., Amedei, A., D'Elios, M. M., Telford, J. L., & Baldari, C. T.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2003-12-15
- Volume
- 198
- Issue
- 12
- Pages
- 1887-1897
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2108650847
- Cited by
- 302
- References
- 1
- FWCI
- 23.50
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Boncristiano, M., Paccani, S. R., Barone, S., Ulivieri, C., Patrussi, L., Ilver, D., Amedei, A., D'Elios, M. M., Telford, J. L., & Baldari, C. T. (2003). The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20030621
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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