The Liver May Act as a Firewall Mediating Mutualism Between the Host and Its Gut Commensal Microbiota

被引:353
作者
Balmer, Maria L. [1 ]
Slack, Emma [1 ]
de Gottardi, Andrea [1 ]
Lawson, Melissa A. E. [1 ]
Hapfelmeier, Siegfried [2 ]
Miele, Luca [3 ]
Grieco, Antonio [3 ]
Van Vlierberghe, Hans [4 ]
Fahrner, Rene [1 ]
Patuto, Nicola [1 ]
Bernsmeier, Christine [5 ]
Ronchi, Francesca [1 ]
Wyss, Madeleine [1 ]
Stroka, Deborah [1 ]
Dickgreber, Nina [6 ]
Heim, Markus H. [5 ]
Mccoy, Kathy D. [1 ]
Macpherson, Andrew J. [1 ]
机构
[1] Univ Bern, Univ Klin Viszerale Chirurg & Med, Inselspital, Maurice Muller Labs DKF, CH-3010 Bern, Switzerland
[2] Univ Bern, Inst Infect Dis, CH-3010 Bern, Switzerland
[3] Univ Cattolica Sacro Cuore, Inst Internal Med, I-00168 Rome, Italy
[4] Univ Ghent, Dept Gastroenterol & Hepatol, B-9000 Ghent, Belgium
[5] Univ Basel Hosp, Div Gastroenterol & Hepatol, CH-4031 Basel, Switzerland
[6] Univ Bern, Inst Pathol, CH-3010 Bern, Switzerland
基金
瑞士国家科学基金会; 加拿大健康研究院; 欧洲研究理事会;
关键词
FATTY LIVER; KUPFFER CELLS; MOUSE MODELS; GERM-FREE; DISEASE; CIRRHOSIS; BACTERIA; RATS; MICE; IGA;
D O I
10.1126/scitranslmed.3008618
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 inmice 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.
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页数:10
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