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Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion
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 T(reg) cells. We have previously shown that H. pylori upregulates B7-H1 expression on GEC, which, in turn, suppress T cell prolifera...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373751/ https://www.ncbi.nlm.nih.gov/pubmed/25807464 http://dx.doi.org/10.1371/journal.pone.0121841 |
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author | Lina, Taslima T. Alzahrani, Shatha House, Jennifer Yamaoka, Yoshio Sharpe, Arlene H. Rampy, Bill A. Pinchuk, Irina V. Reyes, Victor E. |
author_facet | Lina, Taslima T. Alzahrani, Shatha House, Jennifer Yamaoka, Yoshio Sharpe, Arlene H. Rampy, Bill A. Pinchuk, Irina V. Reyes, Victor E. |
author_sort | Lina, Taslima T. |
collection | PubMed |
description | 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 T(reg) 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 T(reg) 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 T(reg) cells in the stomach, increased IL-10 in the serum. Interestingly, B7-H1(-/-) mice showed less T(reg) 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 T(reg) cell induction; thus, contribute to establishing a persistent infection characteristic of H. pylori. |
format | Online Article Text |
id | pubmed-4373751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43737512015-03-27 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. PLoS One Research Article 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 T(reg) 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 T(reg) 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 T(reg) cells in the stomach, increased IL-10 in the serum. Interestingly, B7-H1(-/-) mice showed less T(reg) 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 T(reg) cell induction; thus, contribute to establishing a persistent infection characteristic of H. pylori. Public Library of Science 2015-03-25 /pmc/articles/PMC4373751/ /pubmed/25807464 http://dx.doi.org/10.1371/journal.pone.0121841 Text en © 2015 Lina et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article 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 |
title |
Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion |
title_full |
Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion |
title_fullStr |
Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion |
title_full_unstemmed |
Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion |
title_short |
Helicobacter pylori cag Pathogenicity Island's Role in B7-H1 Induction and Immune Evasion |
title_sort | helicobacter pylori cag pathogenicity island's role in b7-h1 induction and immune evasion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373751/ https://www.ncbi.nlm.nih.gov/pubmed/25807464 http://dx.doi.org/10.1371/journal.pone.0121841 |
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