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.

A gut-vascular barrier controls the systemic dissemination of bacteria / I. Spadoni, E. Zagato, A. Bertocchi, R. Paolinelli, E. Hot, A. Di Sabatino, F. Caprioli, L. Bottiglieri, A. Oldani, G. Viale, G. Penna, E. Dejana, M. Rescigno. - In: SCIENCE. - ISSN 0036-8075. - 350:6262(2015 Nov 13), pp. 830-834. [10.1126/science.aad0135]

A gut-vascular barrier controls the systemic dissemination of bacteria

I. Spadoni
Primo
;
E. Zagato
Secondo
;
A. Bertocchi;F. Caprioli;G. Viale;E. Dejana
Penultimo
;
M. Rescigno
Ultimo
2015

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.
Settore MED/08 - Anatomia Patologica
Settore MED/12 - Gastroenterologia
Settore MED/04 - Patologia Generale
Settore BIO/13 - Biologia Applicata
13-nov-2015
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/334935
Citazioni
  • ???jsp.display-item.citation.pmc??? 223
  • Scopus 408
  • ???jsp.display-item.citation.isi??? 377
social impact