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.
2003
198
1887
1897
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.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/213708
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