CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection

Taslima T. Lina, Iryna Pinchuk, Jennifer House, Yoshio Yamaoka, David Y. Graham, Ellen J. Beswick, Victor Reyes

Research output: Contribution to journalArticle

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Abstract

Gastric epithelial cells (GECs) are the primary target for Helicobacter pylori infection and may act as APCs regulating local T cell responses. We previously reported that H. pylori infection of GECs induces the expression of the T cell coinhibitory molecule B7-H1 on GECs. This process contributes to the hyporesponsiveness of CD4+ effector T cells and accumulation of regulatory T cells. In the present study, we investigated the impact of H. pylori cytotoxin-associated gene A (CagA) on the modulation of the expression of the T cell costimulator B7-H2 by GECs. B7-H2 is involved in promoting Th17 type responses. H. pylori infection downregulates B7-H2 expression by GECs in a CagA-dependent manner. IFN-γ, which is increased in the H. pylori-infected gastric mucosa, synergizes with H. pylori in downregulating B7-H2 expression by GECs. CagA-mediated modulation of B7-H2 on GECs involves p70 S6 kinase phosphorylation. The CagA-dependent B7-H2 downregulation in GECs correlates with a decrease in Th17 type responses in vitro and in vivo. Furthermore, CagA-dependent modulation of Th17 responses was inversely correlated with the H. pylori colonization levels in vivo. Our data suggest that CagA contributes to the ability of H. pylori to evade Th17-mediated clearance by modulating expression of B7-H2 and, thus, to the establishment of the H. pylori chronic infection.

Original languageEnglish (US)
Pages (from-to)3838-3846
Number of pages9
JournalJournal of Immunology
Volume191
Issue number7
DOIs
StatePublished - Oct 1 2013

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Cytotoxins
Helicobacter Infections
Gastric Mucosa
Helicobacter pylori
Down-Regulation
Stomach
Epithelial Cells
Genes
T-Lymphocytes
B7 Antigens
70-kDa Ribosomal Protein S6 Kinases
Regulatory T-Lymphocytes
Phosphorylation
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection. / Lina, Taslima T.; Pinchuk, Iryna; House, Jennifer; Yamaoka, Yoshio; Graham, David Y.; Beswick, Ellen J.; Reyes, Victor.

In: Journal of Immunology, Vol. 191, No. 7, 01.10.2013, p. 3838-3846.

Research output: Contribution to journalArticle

Lina, Taslima T. ; Pinchuk, Iryna ; House, Jennifer ; Yamaoka, Yoshio ; Graham, David Y. ; Beswick, Ellen J. ; Reyes, Victor. / CagA-dependent downregulation of B7-H2 expression on gastric mucosa and inhibition of Th17 responses during Helicobacter pylori infection. In: Journal of Immunology. 2013 ; Vol. 191, No. 7. pp. 3838-3846.
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