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1. Mucosal Associated Invariant T cells in the human gastric mucosa and blood: Role in Helicobacter pylori infection

Author

Jayaum S Booth, Rosangela eSalerno-Goncalves, Thomas G Blanchard, Seema A. Patil, Howard A. Kader, Anca M. Safta, Lindsay M. Morningstar, Steven J. Czinn, Bruce D. Greenwald, and Marcelo B. Sztein

Subjects
Stomach, cytotoxic, H. pylori, age-related, gastric MAIT, Immunologic diseases. Allergy, RC581-607
Abstract

Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial innate-like T cells that have been characterized in human blood, liver, lungs and intestine. Here, we investigated, for the first time, the presence of MAIT cells in the stomach of children, adults and the elderly undergoing routine endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori-Hp), a major gastric pathogen. We observed that MAIT cells are present in the lamina propria compartment of the stomach and display a similar memory phenotype to blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able to recognize H. pylori. We found that CD8+ and CD4-CD8- (DN) MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1 restrictive manner by producing cytokines (IFNg, TNFa, IL-17A) and exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell frequency in Hp+ve individuals was significantly lower than in Hp-ve individuals. However, gastric MAIT cell frequency was not significantly different between Hp+ve and Hp-ve individuals, demonstrating a dichotomy between blood and gastric tissues. Further, we observed that the majority of gastric MAIT cells (>80%) expressed tissue-resident markers (CD69+ CD103+), which were only marginally present on PBMC MAIT cells (

Published
2015
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2. Genome Sequences of 65 Helicobacter pylori Strains Isolated from Asymptomatic Individuals and Patients with Gastric Cancer, Peptic Ulcer Disease, or Gastritis

Author

Yang Song, Sean C. Daugherty, Ankit Maroo, W. Florian Fricke, Monika Keelan, Carri McCracken, Steven J. Czinn, Pelayo Correa, Claire M. Fraser, Kent Shefchek, Teruko Nakazawa, Lindsay M. Morningstar, Thomas G. Blanchard, and Ivette Santana-Cruz

Subjects
Microbiology (medical), Adult, DNA, Bacterial, medicine.medical_specialty, Peptic Ulcer, Molecular Sequence Data, Disease, Colombia, Gastroenterology, Article, Helicobacter Infections, Japan, Stomach Neoplasms, Internal medicine, Genotype, medicine, Gastric mucosa, Immunology and Allergy, Cluster Analysis, Humans, Phylogeny, Asymptomatic Diseases, General Immunology and Microbiology, biology, Helicobacter pylori, Cancer, General Medicine, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Infectious Diseases, medicine.anatomical_structure, Gastritis, Immunology, North America, Host adaptation, medicine.symptom, Genome, Bacterial
Abstract

Helicobacter pylori, inhabitant of the gastric mucosa of over half of the world population, with decreasing prevalence in the U.S., has been associated with a variety of gastric pathologies. However, the majority of H. pylori infected individuals remain asymptomatic and negative correlations between H. pylori and allergic diseases have been reported. Comprehensive genome characterization of H. pylori populations from different human host backgrounds including healthy individuals provides the exciting potential to generate new insights into the open question whether human health outcome is associated with specific H. pylori genotypes or dependent on other environmental factors. We report the genome sequences of 65 Helicobacter pylori isolates from individuals with gastric cancer, preneoplastic lesions, peptic ulcer disease, gastritis, and from asymptomatic adults. Isolates were collected from multiple locations in North America (USA and Canada) as well as from Columbia and Japan. The availability of these H. pylori genome sequences from individuals with distinct clinical presentations provides the research community with a resource for detailed investigations into genetic elements that correlate either positively or negatively with the epidemiology, human host adaptation and gastric pathogenesis, and will aid in the characterization of strains that may favor the development of specific pathology, including gastric cancer.

Published
2013

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