Document Detail


The intermediate region of Helicobacter pylori VacA is a determinant of toxin potency in a Jurkat T cell assay.
MedLine Citation:
PMID:  22585965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Colonization of the human stomach with Helicobacter pylori is a risk factor for peptic ulceration, noncardia gastric adenocarcinoma, and gastric lymphoma. The secreted VacA toxin is an important H. pylori virulence factor that causes multiple alterations in gastric epithelial cells and T cells. Several families of vacA alleles have been described, and H. pylori strains containing certain vacA types (s1, i1, and m1) are associated with an increased risk of gastric disease, compared to strains containing other vacA types (s2, i2, and m2). Thus far, there has been relatively little study of the role of the VacA intermediate region (i-region) in toxin activity. In this study, we compared the ability of i1 and i2 forms of VacA to cause functional alterations in Jurkat cells. To do this, we manipulated the chromosomal vacA gene in two H. pylori strains to introduce alterations in the region encoding the VacA i-region. We did not detect any differences in the capacity of i1 and i2 forms of VacA to cause vacuolation of RK13 cells. In comparison to i1 forms of VacA, i2 forms of VacA had a diminished capacity to inhibit the activation of nuclear factor of activated T cells (NFAT) and suppress interleukin-2 (IL-2) production. Correspondingly, i2 forms of VacA bound to Jurkat cells less avidly than did i1 forms of VacA. These results indicate that the VacA i-region is an important determinant of VacA effects on human T cell function.
Authors:
Christian González-Rivera; Holly M Scott Algood; Jana N Radin; Mark S McClain; Timothy L Cover
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-05-14
Journal Detail:
Title:  Infection and immunity     Volume:  80     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-19     Completed Date:  2012-10-10     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2578-88     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antigens, CD18 / metabolism
Bacterial Proteins / metabolism*,  toxicity*
Gene Expression Regulation, Bacterial / physiology*
Helicobacter pylori / metabolism*
Humans
Interleukin-2 / metabolism
Jurkat Cells
Molecular Sequence Data
Protein Binding
Protein Isoforms
T-Lymphocytes / immunology,  metabolism*,  microbiology
Grant Support
ID/Acronym/Agency:
AI039657/AI/NIAID NIH HHS; AI068009/AI/NIAID NIH HHS; DK058404/DK/NIDDK NIH HHS; R01 AI039657/AI/NIAID NIH HHS; R25 GM062459/GM/NIGMS NIH HHS; T32 AI007281-21/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD18; 0/Bacterial Proteins; 0/Interleukin-2; 0/Protein Isoforms; 0/VacA protein, Helicobacter pylori
Comments/Corrections

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