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: Ilaria Spadoni, Elena Zagato, Alice Bertocchi, Roberta Paolinelli, Edina Hot, Antonio Di Sabatino, Flavio Caprioli, Luca Bottiglieri, Amanda Oldani, Giuseppe Viale, Giuseppe Penna, Elisabetta Dejana, Maria Rescigno
• Journal: Science (New York, N.Y.) (Science) Vol. 350 Issue 6262 Pg. 830-4 (Nov 13 2015) ISSN: 1095-9203 [Electronic] United States
• PMID: 26564856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Association for the Advancement of Science.

Chemical References

• Antigens, Bacterial
• Type III Secretion Systems
• beta Catenin
• Transaminases

Topics

• Animals
• Antigens, Bacterial (blood, immunology)
• Capillary Permeability (immunology)
• Celiac Disease (blood, immunology, microbiology)
• Genomic Islands (genetics, immunology)
• Humans
• Ileum (blood supply, immunology, microbiology)
• Intestinal Mucosa (immunology, microbiology)
• Intestines (blood supply, immunology, microbiology)
• Liver (immunology)
• Mice
• Mice, Inbred C57BL
• Microbiota (immunology)
• Salmonella Infections (immunology)
• Salmonella typhimurium (genetics, immunology, pathogenicity)
• Signal Transduction
• Spleen (immunology)
• Transaminases (blood)
• Type III Secretion Systems (genetics, immunology)
• Wnt Signaling Pathway
• beta Catenin (metabolism)