The Journal of Experimental Medicine
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 15 December 2003. doi:10.1084/jem.20030621
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Boncristiano, M.
Right arrow Articles by Baldari, C. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boncristiano, M.
Right arrow Articles by Baldari, C. T.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CALCIUM COMPOUNDS
*CALCIUM, ELEMENTAL
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/12/1887 $5.00
The Journal of Experimental Medicine, Volume 198, Number 12, 1887-1897

The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms

Marianna Boncristiano1, Silvia Rossi Paccani1, Silvia Barone2, Cristina Ulivieri1, Laura Patrussi1, Dag Ilver2, Amedeo Amedei3, Mario Milco D'Elios3, John L. Telford2 and Cosima T. Baldari1

1 Department of Evolutionary Biology, University of Siena, 53100 Siena, Italy
2 IRIS, Chiron Vaccines, 53100 Siena, Italy
3 Department of Internal Medicine and Immunoallergology, University of Florence, 50134 Florence, Italy

Address correspondence to John L. Telford, IRIS, Chiron Vaccines, Via Fiorentina 1, 53100 Siena, Italy. Phone: 39-0577-243470; Fax: 39-0577-243564; email: john_telford{at}chiron.it

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.

Key Words: MAP kinase signaling cascades • immunosuppression • host–pathogen interactions • calcium signaling

M. Boncristiano and S. Rossi Paccani contributed equally to this work.

D. Ilver's present address is Institute of Medical Biochemistry, Göteborg University, 40530 Göteborg, Sweden.

Abbreviations used in this paper: COX, cyclooxygenase; MAPK, mitogen-activated protein kinase; NPPB, 5-nitro-2-(3-phenylpropylamino)-benzoic acid.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS