Publikation

The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota

Wissenschaftlicher Artikel/Review - 21.05.2014

Bereiche
PubMed
DOI

Zitation
Balmer M, McCoy K, Heim M, Dickgreber N, Stroka D, Wyss M, Ronchi F, Bernsmeier C, Patuto N, Fahrner R, Van Vlierberghe H, Grieco A, Miele L, Hapfelmeier S, Lawson M, De Gottardi A, Slack E, Macpherson A. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci Transl Med 2014; 6:237ra66.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Sci Transl Med 2014; 6
Veröffentlichungsdatum
21.05.2014
eISSN (Online)
1946-6242
Seiten
237ra66
Kurzbeschreibung/Zielsetzung

A prerequisite for establishment of mutualism between the host and the microbial community that inhabits the large intestine is the stringent mucosal compartmentalization of microorganisms. Microbe-loaded dendritic cells trafficking through lymphatics are arrested at the mesenteric lymph nodes, which constitute the firewall of the intestinal lymphatic circulation. We show in different mouse models that the liver, which receives the intestinal venous blood circulation, forms a vascular firewall that captures gut commensal bacteria entering the bloodstream during intestinal pathology. Phagocytic Kupffer cells in the liver of mice clear commensals from the systemic vasculature independently of the spleen through the liver's own arterial supply. Damage to the liver firewall in mice impairs functional clearance of commensals from blood, despite heightened innate immunity, resulting in spontaneous priming of nonmucosal immune responses through increased systemic exposure to gut commensals. Systemic immune responses consistent with increased extraintestinal commensal exposure were found in humans with liver disease (nonalcoholic steatohepatitis). The liver may act as a functional vascular firewall that clears commensals that have penetrated either intestinal or systemic vascular circuits.