The Journal of experimental medicine, 2003-12, Vol.198 (12), p.1887-1897
2003
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Details
- Autor(en) / Beteiligte
- Titel
- The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms
- Ist Teil von
- The Journal of experimental medicine, 2003-12, Vol.198 (12), p.1887-1897
- Ort / Verlag
- United States: The Rockefeller University Press
- Erscheinungsjahr
- 2003
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1007eISSN: 1540-9538DOI: 10.1084/jem.20030621Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2194151
- Format
- –
- Schlagworte
- actin, Active Transport, Cell Nucleus, Bacterial Proteins - toxicity, Calcium - metabolism, Calcium-Calmodulin-Dependent Protein Kinases - physiology, DNA-Binding Proteins - antagonists & inhibitors, DNA-Binding Proteins - metabolism, Helicobacter pylori, Helicobacter pylori - pathogenicity, Humans, Immunosuppressive Agents - toxicity, Jurkat Cells, Lymphocyte Activation - drug effects, Macrophages - drug effects, Macrophages - enzymology, MAP Kinase Kinase 3, MAP Kinase Kinase 6, Mitogen-Activated Protein Kinase Kinases - physiology, Mitogen-Activated Protein Kinases - physiology, Neutrophils - drug effects, Neutrophils - enzymology, NF-AT protein, NFATC Transcription Factors, Nuclear Proteins, p38 Mitogen-Activated Protein Kinases, Protein-Tyrosine Kinases - physiology, Signal Transduction, T-Lymphocytes - drug effects, T-Lymphocytes - immunology, Transcription Factors - antagonists & inhibitors, Transcription Factors - metabolism, VacA protein