論文 - 詳細
| RRC ID | 67721 |
|---|---|
| 著者 | Lina TT, Alzahrani S, House J, Yamaoka Y, Sharpe AH, Rampy BA, Pinchuk IV, Reyes VE. |
| タイトル | Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion. |
| ジャーナル | PLoS One |
| 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 vivo confirmation 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. |
| 巻・号 | 10(3) |
| ページ | e0121841 |
| 公開日 | 2015-1-1 |
| DOI | 10.1371/journal.pone.0121841 |
| PII | PONE-D-14-33107 |
| PMID | 25807464 |
| PMC | PMC4373751 |
| MeSH | Animals B7-H1 Antigen / immunology B7-H1 Antigen / metabolism* Cell Proliferation Gastric Mucosa / immunology Gastric Mucosa / metabolism Genomic Islands* Helicobacter Infections / immunology Helicobacter Infections / metabolism Helicobacter Infections / microbiology Helicobacter pylori / genetics* Helicobacter pylori / metabolism Immune Evasion / genetics* Interleukin-10 / metabolism Mice Signal Transduction T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / metabolism Up-Regulation |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HGC-27(RCB0500) |