title: Helicobacter pylori γ-Glutamyltranspeptidase Induces Tolerogenic Human Dendritic Cells by Activation of Glutamate Receptors.
abstract: Helicobacter pylori infection is characterized by chronic persistence of the bacterium. Different virulence factors, including H. pylori γ-glutamyltranspeptidase (gGT), have been reported to induce tolerogenicity by reprogramming dendritic cells (DCs). gGT is present in all bacterial isolates, indicating an important role for gGT in the course of infection. In the current study, we have analyzed the effect of H. pylori gGT on human DCs and the subsequent adaptive immune response. We show that glutamate produced due to H. pylori gGT enzymatic activity tolerizes DCs by inhibiting cAMP signaling and dampening IL-6 secretion in response to the infection. Together, our results provide a novel molecular mechanism by which H. pylori manipulates the host's immune response to persist within its host.
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany; and.
authors.forename: Romy
authors.initials: R
authors.lastname: Käbisch
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany; and.
authors.forename: Raphaela P
authors.identifier: 0000-0001-8697-0638
authors.initials: RP
authors.lastname: Semper
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany; and.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wüstner
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany; and German Centre for Infection Research, 81675 Munich, Germany.
authors.forename: Markus
authors.identifier: 0000-0001-9110-3950
authors.initials: M
authors.lastname: Gerhard
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, 81675 Munich, Germany; and raquel.mejias-luque@tum.de.
authors.forename: Raquel
authors.identifier: 0000-0002-4602-4927
authors.initials: R
authors.lastname: Mejías-Luque
mesh_terms: D056704:Adaptive Immunity; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology; D005723:gamma-Glutamyltransferase / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D017470:Receptors, Glutamate; D037521:Virulence Factors; D000242:Cyclic AMP; D005723:gamma-Glutamyltransferase