title: Interaction between intestinal dendritic cells and bacteria translocated from the gut in rats with cirrhosis.
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 CCl(4) induced in rats. To examine their activation state and functions, DCs (CD103(+) RT1B(+) CD3(-) CD45RA(-) ) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Medicina, Universidad de Alcalá, Madrid, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Muñoz
authors.forename: María
authors.initials: M
authors.lastname: José Borrero
authors.forename: María
authors.initials: M
authors.lastname: Ubeda
authors.forename: Margaret
authors.initials: M
authors.lastname: Lario
authors.forename: David
authors.initials: D
authors.lastname: Díaz
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
authors.forename: Jorge
authors.initials: J
authors.lastname: Monserrat
authors.forename: Oscar
authors.initials: O
authors.lastname: Pastor
authors.forename: Elia
authors.initials: E
authors.lastname: Aguado-Fraile
authors.forename: José
authors.initials: J
authors.lastname: Such
authors.forename: Melchor
authors.initials: M
authors.lastname: Alvarez-Mon
authors.forename: Agustín
authors.initials: A
authors.lastname: Albillos
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D001201:Ascites / Q000139:chemically induced / Q000276:immunology; D018988:Bacterial Translocation / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002251:Carbon Tetrachloride; D002465:Cell Movement; D049109:Cell Proliferation; D004269:DNA, Bacterial / Q000276:immunology / Q000302:isolation & purification; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D039001:Integrin alpha Chains / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008643:Mesentery; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D015704:CD4 Antigens; D004269:DNA, Bacterial; D039001:Integrin alpha Chains; D014409:Tumor Necrosis Factor-alpha; C091367:alpha E integrins; D002251:Carbon Tetrachloride