title: A gut-vascular barrier controls the systemic dissemination of bacteria.
abstract: In healthy individuals, the intestinal microbiota cannot access the liver, spleen, or other peripheral tissues. Some pathogenic bacteria can reach these sites, however, and can induce a systemic immune response. How such compartmentalization is achieved is unknown. We identify a gut-vascular barrier (GVB) in mice and humans that controls the translocation of antigens into the blood stream and prohibits entry of the microbiota. Salmonella typhimurium can penetrate the GVB in a manner dependent on its pathogenicity island (Spi) 2-encoded type III secretion system and on decreased β-catenin-dependent signaling in gut endothelial cells. The GVB is modified in celiac disease patients with elevated serum transaminases, which indicates that GVB dismantling may be responsible for liver damage in these patients. Understanding the GVB may provide new insights into the regulation of the gut-liver axis.
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Spadoni
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Zagato
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bertocchi
authors.affiliation: The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Paolinelli
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Edina
authors.initials: E
authors.lastname: Hot
authors.affiliation: First Department of Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.affiliation: Unità Operativa Gastroenterologia ed Endoscopia, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico di Milano, and Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.affiliation: Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bottiglieri
authors.affiliation: The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy.
authors.forename: Amanda
authors.initials: A
authors.lastname: Oldani
authors.affiliation: Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penna
authors.affiliation: The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy. Department of Biosciences, Università degli Studi di Milano, Italy. Department of Genetics, Immunology and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Department of Biosciences, Università degli Studi di Milano, Italy. maria.rescigno@ieo.eu.
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology*; D002446:Celiac Disease / Q000097:blood / Q000276:immunology / Q000382:microbiology; D044404:Genomic Islands / Q000235:genetics / Q000276:immunology; D006801:Humans; D007082:Ileum / Q000098:blood supply / Q000276:immunology / Q000382:microbiology; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000098:blood supply / Q000276:immunology* / Q000382:microbiology*; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D000637:Transaminases / Q000097:blood; D000069296:Type III Secretion Systems / Q000235:genetics / Q000276:immunology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D000069296:Type III Secretion Systems; D051176:beta Catenin; D000637:Transaminases