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.
The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms / BONCRISTIANO M.; PACCANI S.R.; BARONE S.; ULIVIERI C.; PATRUSSI L.; ILVER D.; A. AMEDEI; D'ELIOS M.M.; TELFORD J.L.; BALDARI C.T.. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - STAMPA. - 198:(2003), pp. 1887-1897. [10.1084/jem.20030621]
The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms.
AMEDEI, AMEDEO;D'ELIOS, MARIO MILCO;
2003
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms.pdf
Accesso chiuso
Tipologia:
Pdf editoriale (Version of record)
Licenza:
Tutti i diritti riservati
Dimensione
421.58 kB
Formato
Adobe PDF
|
421.58 kB | Adobe PDF | Richiedi una copia |
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.