title: Propionibacterium acnes overabundance and natural killer group 2 member D system activation in corpus-dominant lymphocytic gastritis.
abstract: Corpus-dominant lymphocytic gastritis (LyG) is characterized by CD8+T-cell infiltration of the stomach epithelium by a so far uncharacterized mechanism. Although Helicobacter pylori is typically undetectable in LyG, patients respond to H. pylori antibiotic eradication therapy, suggesting a non-H. pylori microbial trigger for the disease. Comparative microbiota analysis of specimens from LyG, H. pylori gastritis and healthy controls precluded involvement of H. pylori in LyG but identified Propionibacterium acnes as a possible disease trigger. In addition, the natural killer group 2 member D (NKG2D) system and the proinflammatory cytokine interleukin (IL)-15 are significantly upregulated in the gastric mucosa of LyG patients, and gastric epithelial cells respond to microbe-derived stimuli, including live P. acnes and the microbial products short-chain fatty acids, with induction of NKG2D ligands. In contrast, H. pylori infection does not activate or even repress NKG2D ligands. Together, our findings identify P. acnes as a possible causative agent for LyG, which is dependent on the NKG2D system and IL-15 activation. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Montalban-Arques
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Wurm
authors.affiliation: Centre for Medical Research, Medical University of Graz, Graz, Austria.
authors.forename: Slave
authors.initials: S
authors.lastname: Trajanoski
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schauer
authors.affiliation: Institute of Molecular Biosciences, University of Graz, Graz, Austria.|BioTechMed, Interuniversity Cooperation, Graz, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Kienesberger
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.|BioTechMed, Interuniversity Cooperation, Graz, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Halwachs
authors.affiliation: Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.|Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Högenauer
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.|Theodor Escherich Laboratory for Medical Microbiome Research, Medical University of Graz, Graz, Austria.|BioTechMed, Interuniversity Cooperation, Graz, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Gorkiewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D019409:Interleukin-15 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008218:Lymphocytosis / Q000276:immunology / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D011425:Propionibacterium acnes / Q000276:immunology / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000235:genetics; D013270:Stomach / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D019409:Interleukin-15; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D012333:RNA, Messenger
keywords: 16S rRNA gene; Helicobacter pylori; IL-15; MICA; NKG2D; Propionibacterium acnes; gastric epithelial cells; intraepithelial lymphocytes; lymphocytic gastritis; short-chain fatty acids; stomach microbiota