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Comment
. 2003 Dec 15;198(12):1767-71.
doi: 10.1084/jem.20031839.

Immunosuppressive and proinflammatory activities of the VacA toxin of Helicobacter pylori

Cesare Montecucco  1 , Marina de Bernard
Affiliations
Comment

Immunosuppressive and proinflammatory activities of the VacA toxin of Helicobacter pylori

Cesare Montecucco et al. J Exp Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
VacA inhibits T cell activation and proliferation via two mechanisms. The first is linked to the anion-selective channel activity of this toxin which depolarizes the plasma membrane and prevents the opening of the CRAC calcium channel, which is operated by the calcium released from intracellular stores. At low cytosolic calcium, the phosphatase calcineurin does not dephosphorylate NFAT, thus preventing its translocation into the nucleus and the activation of the expression of IL-2 and IL-2 receptor necessary for proliferation. In addition, low doses of VacA or its COOH-terminal domain p58 (top right side) inhibit T cell activation by inducing a cascade of phosphorylation events involving a still unidentified protein (brown), Vav, and MKK3/6, resulting in an increase of the active form of p38, but not of Erk, which may induce anergy. In addition Vav induces actin rearrangement through the small GTPase Rac, which leads to inhibition of T cell proliferation.
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