Interaction between intestinal dendritic cells and bacteria translocated from the gut in rats with cirrhosis

Authors

  • Leticia Muñoz,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • María José Borrero,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • María Ubeda,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • Margaret Lario,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • David Díaz,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • Rubén Francés,

    1. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
    2. Hospital General Universitario de Alicante, Alicante, Spain
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  • Jorge Monserrat,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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  • Óscar Pastor,

    1. Servicio de Bioquímica Clínica, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
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  • Elia Aguado-Fraile,

    1. Servicio de Anatomía Patológica, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
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  • José Such,

    1. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
    2. Hospital General Universitario de Alicante, Alicante, Spain
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  • Melchor Álvarez-Mon,

    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
    3. Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
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    • These authors shared senior authorship in this work.

  • Agustín Albillos

    Corresponding author
    1. Departamento de Medicina, Universidad de Alcalá, Madrid, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
    3. Servicio de Gastroenterología, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain
    • Departamento de Medicina, Facultad de Medicina-Campus Universitario, Universidad de Alcalá, Carretera Madrid-Barcelona km. 33.600, 28871 Alcalá de Henares, Madrid, Spain
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    • fax: +34918854526;


  • Potential conflict on interest: Nothing to report.

Abstract

Cirrhosis with ascites is associated with a high rate of gut bacterial translocation (GBT) and spontaneous bacterial infections of enteric origin. We addressed the activation state and role of intestinal dendritic cells (DCs) in experimental ascitic cirrhosis and their relationship with GBT. Cirrhosis with ascites was CCl4 induced in rats. To examine their activation state and functions, DCs (CD103+RT1B+CD3CD45RA) were isolated from the intestinal lamina propria and mesenteric lymph nodes (MLNs), and the following parameters were determined by flow cytometry: surface antigen expression; spontaneous or lipopolysaccharide-stimulated tumor necrosis factor alpha (TNF-α) production; and in vitro capacity to phagocytose latex beads and to migrate toward the chemokine (C-C motif) ligand 21. GBT was defined as the growth of bacteria in MLNs culture. Bacterial DNA (Bact-DNA) in MLNs was identified by polymerase chain reaction. In rats with Bact-DNA in MLNs without GBT, intestinal and MLNs CD103+-DCs showed features of activation, expansion of the proinflammatory CD4+-DC subpopulation, augmented TNF-α production, and increased phagocytic and migratory capacities. In contrast, in rats with GBT, CD103+-DCs showed the absence of an activated phenotype, lowered TNF-α production, and relatively deficient phagocytosis and migration capacities. The CD103+-DC of rats without Bact-DNA in MLNs or GBT were similar to controls. In cirrhotic rats, bowel decontamination with antibiotics eliminated Bact-DNA in MLNs and GBT, normalized the activation state and functions of CD103+-DCs, and increased their TNF-α production. Conclusion: In experimental cirrhosis with ascites, continuous pressure of gut bacteria shapes the phenotypic and functional profile of intestinal DCs to produce effects that range from their activation and enhanced functions to their exhaustion and tolerance. (HEPATOLOGY 2012;56:1861–1869)

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