title: Mucosal Inducible NO Synthase-Producing IgA+ Plasma Cells in Helicobacter pylori-Infected Patients.
abstract: The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)-dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori-infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS(+) cell population in H. pylori-infected patients and confirmed intracellular NO production. Because we did not detect iNOS(+) PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS(+) PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA(+) PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS(+) PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany; thomas.schneider@charite.de.
authors.forename: Laura
authors.identifier: 0000-0002-7870-7722
authors.initials: L
authors.lastname: Neumann
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
authors.forename: Mattea
authors.identifier: 0000-0002-3340-5122
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
authors.forename: Verena
authors.initials: V
authors.lastname: Moos
authors.affiliation: Practice for Gastroenterology, 12163 Berlin, Germany;
authors.forename: Frank
authors.initials: F
authors.lastname: Heller
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Meyer
authors.affiliation: PathoTres Practice for Pathology, 12247 Berlin, Germany;
authors.forename: Christoph
authors.identifier: 0000-0001-8695-8081
authors.initials: C
authors.lastname: Loddenkemper
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Bojarski
authors.affiliation: Department of Molecular Biology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Fehlings
authors.affiliation: Department of Medicine, Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, 10117 Berlin, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Doerner
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
authors.forename: Kristina
authors.initials: K
authors.lastname: Allers
authors.affiliation: Robert Koch Institute, 13302 Berlin, Germany; and.
authors.forename: Toni
authors.initials: T
authors.lastname: Aebischer
authors.affiliation: Institute for Microbiology and Hygiene, Charité-University Medicine Berlin, 12203 Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
authors.affiliation: Medical Clinic I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-University Medicine Berlin, 12203 Berlin, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider
mesh_terms: D001706:Biopsy; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D007150:Immunohistochemistry; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D010950:Plasma Cells / Q000201:enzymology* / Q000276:immunology*; D011446:Prospective Studies; D011706:Pyloric Antrum / Q000382:microbiology / Q000473:pathology
chemical_list: D007070:Immunoglobulin A; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II