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Science. 2015 Nov 13;350(6262):830-4. doi: 10.1126/science.aad0135.

A gut-vascular barrier controls the systemic dissemination of bacteria.

Author information

1
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
2
The Italian Foundation for Cancer Research (FIRC) Institute of Molecular Oncology (IFOM), Milan, Italy.
3
First Department of Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy.
4
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.
5
Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy.
6
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.
7
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Department of Biosciences, Università degli Studi di Milano, Italy. maria.rescigno@ieo.eu.

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.

PMID:
26564856
DOI:
10.1126/science.aad0135
[Indexed for MEDLINE]
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