A gut-vascular barrier controls the systemic dissemination of bacteria

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...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 350; no. 6262; pp. 830 - 834
Main Authors:	Spadoni, Ilaria, Zagato, Elena, Bertocchi, Alice, Paolinelli, Roberta, Hot, Edina, Di Sabatino, Antonio, Caprioli, Flavio, Bottiglieri, Luca, Oldani, Amanda, Viale, Giuseppe, Penna, Giuseppe, Dejana, Elisabetta, Rescigno, Maria
Format:	Journal Article
Language:	English
Published:	United States 13.11.2015
Subjects:	Animals Antigens, Bacterial - blood Antigens, Bacterial - immunology beta Catenin - metabolism Capillary Permeability - immunology Celiac Disease - blood Celiac Disease - immunology Celiac Disease - microbiology Genomic Islands - genetics Genomic Islands - immunology Humans Ileum - blood supply Ileum - immunology Ileum - microbiology Intestinal Mucosa - immunology Intestinal Mucosa - microbiology Intestines - blood supply Intestines - immunology Intestines - microbiology Liver - immunology Mice Mice, Inbred C57BL Microbiota - immunology Salmonella Infections - immunology Salmonella typhimurium - genetics Salmonella typhimurium - immunology Salmonella typhimurium - pathogenicity Signal Transduction Spleen - immunology Transaminases - blood Type III Secretion Systems - genetics Type III Secretion Systems - immunology Wnt Signaling Pathway
ISSN:	1095-9203
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1095-9203
DOI:	10.1126/science.aad0135