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

Antonio Grieco, Maria L. Balmer, Emma Slack, Andrea De Gottardi, Melissa A. E. Lawson, Siegfried Hapfelmeier, Hans Van Vlierberghe, René Fahrner, Nicola Patuto, Christine Bernsmeier, Francesca Ronchi, Madeleine Wyss, Deborah Stroka, Nina Dickgreber, Markus H. Heim, Kathy D. Mccoy, Andrew J. Macpherson

Risultato della ricerca: Contributo in rivistaArticolo in rivista

212 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)237ra66-237ra66
RivistaScience Translational Medicine
Volume6
DOI
Stato di pubblicazionePubblicato - 2014

Keywords

  • Adult
  • Aged
  • Animals
  • Bacterial Load
  • Bacterial Translocation
  • Disease Models, Animal
  • Fatty Liver
  • Feces
  • Female
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Immunity, Mucosal
  • Intestines
  • Kupffer Cells
  • Liver
  • Liver Circulation
  • Liver Diseases
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Retrospective Studies
  • Time Factors

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