Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1126/scitranslmed.3008618

Type

Journal article

Journal

Sci Transl Med

Publication Date

21/05/2014

Volume

6

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, Non-alcoholic Fatty Liver Disease, Retrospective Studies, Time Factors