title: Helicobacter pylori cag pathogenicity island's role in B7-H1 induction and immune evasion.
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.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Taslima T
authors: TT
authors: Lina
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Shatha
authors: S
authors: Alzahrani
authors: Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Jennifer
authors: J
authors: House
authors: Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas, United States Of America.
authors: Yoshio
authors: Y
authors: Yamaoka
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States Of America.
authors: Arlene H
authors: AH
authors: Sharpe
authors: Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Bill A
authors: BA
authors: Rampy
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States Of America; Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Irina V
authors: IV
authors: Pinchuk
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States Of America; Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, United States Of America.
authors: Victor E
authors: VE
authors: Reyes
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism; D044404:Genomic Islands; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000378:metabolism; D057131:Immune Evasion / Q000235:genetics*; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D060890:B7-H1 Antigen; D016753:Interleukin-10