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

Balmer, Maria Luisa; Slack, Emma; De Gottardi, Andrea; Lawson, Melissa; Hapfelmeier, Siegfried Hektor; Miele, Luca; Grieco, Antonio; Van Vlierberghe, Hans; Fahrner, René; Patuto, Nicola; Bernsmeier, Christine; Ronchi, Francesca; Wyss, Madeleine; Keogh-Stroka, Deborah M.; Dickgreber, Nina; Heim, Markus H; McCoy, Kathy D; Macpherson, Andrew (2014). The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Science translational medicine, 6(237), 237ra66. American Association for the Advancement of Science 10.1126/scitranslmed.3008618

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Balmer, Maria Luisa; Slack, Emma; De Gottardi, Andrea; Lawson, Melissa; Hapfelmeier, Siegfried Hektor; Fahrner, René; Ronchi, Francesca; Wyss, Madeleine; Keogh-Stroka, Deborah M. and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1946-6234

Publisher:

American Association for the Advancement of Science

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

23 Feb 2015 11:50

Last Modified:

05 Nov 2015 13:54

Publisher DOI:

10.1126/scitranslmed.3008618

PubMed ID:

24848256

BORIS DOI:

10.7892/boris.63583

URI:

https://boris.unibe.ch/id/eprint/63583

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