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, Irina V. Pinchuk, Victor E. 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

Fingerprint

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

All Science Journal Classification (ASJC) codes

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

Cite this

Lina, T. T., Alzahrani, S., House, J., Yamaoka, Y., Sharpe, A. H., Rampy, B. A., ... Reyes, V. E. (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
Lina, Taslima T. ; Alzahrani, Shatha ; House, Jennifer ; Yamaoka, Yoshio ; Sharpe, Arlene H. ; Rampy, Bill A. ; Pinchuk, Irina V. ; Reyes, Victor E. / 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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Lina, TT, Alzahrani, S, House, J, Yamaoka, Y, Sharpe, AH, Rampy, BA, Pinchuk, IV & Reyes, VE 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

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, Irina V.; Reyes, Victor E.

In: PloS one, Vol. 10, No. 3, e0121841, 25.03.2015.

Research output: Contribution to journalArticle

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AU - Lina, Taslima T.

AU - Alzahrani, Shatha

AU - House, Jennifer

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AU - Sharpe, Arlene H.

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AU - Reyes, Victor E.

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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