Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion

Taslima T. Lina, Shatha Alzahrani, Jennifer House, Yoshio Yamaoka, Arlene H. Sharpe, Bill A. Rampy, Iryna Pinchuk, Victor Reyes

Research output: Contribution to journalArticle

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Abstract

During Helicobacter pylori (H. pylori) infection CD4+ T cells in the gastric lamina propria are hyporesponsive and polarized by Th1/Th17 cell responses controlled by Treg cells. We have previously shown that H. pylori upregulates B7-H1 expression on GEC, which, in turn, suppress T cell proliferation, effector function, and induce Treg cells in vitro. In this study, we investigated the underlying mechanisms and the functional relevance of B7-H1 induction by H. pylori infection to chronic infection. Using H. pylori wild type (WT), cag pathogenicity island (cag PAI-) and cagA- isogenic mutant strains we demonstrated that H. pylori requires its type 4 secretion system (T4SS) as well as its effector protein CagA and peptidoglycan (PG) fragments for B7-H1 upregulation on GEC. Our study also showed that H. pylori uses the p38 MAPK pathway to upregulate B7-H1 expression in GEC. In vivoconfirmation was obtained when infection of C57BL/6 mice with H. pylori PMSS1 strain, which has a functional T4SS delivery system, but not with H. pylori SS1 strain lacking a functional T4SS, led to a strong upregulation of B7-H1 expression in the gastric mucosa, increased bacterial load, induction of Treg cells in the stomach, increased IL-10 in the serum. Interestingly, B7-H1-/-mice showed less Treg cells and reduced bacterial loads after infection. These studies demonstrate how H. pylori T4SS components activate the p38 MAPK pathway, upregulate B7-H1 expression by GEC, and cause Treg cell induction; thus, contribute to establishing a persistent infection characteristic of H. pylori.

Original languageEnglish (US)
Article numbere0121841
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 25 2015

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immune evasion
pathogenicity islands
Immune Evasion
Genomic Islands
Helicobacter pylori
T-cells
p38 Mitogen-Activated Protein Kinases
Regulatory T-Lymphocytes
Up-Regulation
Peptidoglycan
secretion
infection
Cell proliferation
Interleukin-10
Bacterial Load
Helicobacter Infections
cells
Infection
mitogen-activated protein kinase
Stomach

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lina, T. T., Alzahrani, S., House, J., Yamaoka, Y., Sharpe, A. H., Rampy, B. A., ... Reyes, V. (2015). Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. PLoS One, 10(3), [e0121841]. https://doi.org/10.1371/journal.pone.0121841

Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. / Lina, Taslima T.; Alzahrani, Shatha; House, Jennifer; Yamaoka, Yoshio; Sharpe, Arlene H.; Rampy, Bill A.; Pinchuk, Iryna; Reyes, Victor.

In: PLoS One, Vol. 10, No. 3, e0121841, 25.03.2015.

Research output: Contribution to journalArticle

Lina, TT, Alzahrani, S, House, J, Yamaoka, Y, Sharpe, AH, Rampy, BA, Pinchuk, I & Reyes, V 2015, 'Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion', PLoS One, vol. 10, no. 3, e0121841. https://doi.org/10.1371/journal.pone.0121841
Lina TT, Alzahrani S, House J, Yamaoka Y, Sharpe AH, Rampy BA et al. Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. PLoS One. 2015 Mar 25;10(3). e0121841. https://doi.org/10.1371/journal.pone.0121841
Lina, Taslima T. ; Alzahrani, Shatha ; House, Jennifer ; Yamaoka, Yoshio ; Sharpe, Arlene H. ; Rampy, Bill A. ; Pinchuk, Iryna ; Reyes, Victor. / Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. In: PLoS One. 2015 ; Vol. 10, No. 3.
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