title: Role of microbial translocation in soluble CD14 up-regulation in HIV-, but not in HCV-, infected chimpanzees.
abstract: During human immunodeficiency virus (HIV) infection, soluble CD14 (sCD14) is up-regulated as a consequence of pathological disruption of the gut epithelial barrier, and subsequent increased microbial translocation. Also in hepatitis C virus (HCV)-infected patients with advanced liver fibrosis, increased levels of sCD14 have been reported. Since the liver plays an important role in clearance of translocated bacterial products, hepatic fibrosis may negatively affect clearance and thus contribute to higher sCD14 levels. Chimpanzees (Pan troglodytes) infected with HCV typically show no signs of liver fibrosis. Here, we have tested the hypothesis that increased levels of sCD14 occur in the absence of hepatic fibrosis or microbial translocation in chimpanzees chronically infected with HCV. sCD14 was up-regulated in both HIV/simian immunodeficiency virus (SIV)- and HCV-infected chimpanzees. In HIV/SIV-infected chimpanzees, intestinal fatty acid-binding protein, a marker for gut perturbation, lipopolysaccharide (LPS)-binding-protein and LPS core antibodies, confirm that sCD14 up-regulation was caused by increased microbial translocation. In HCV-infected chimpanzees, no evidence was found for increased microbial translocation despite up-regulation of sCD14. Additionally, the impact of liver fibrosis on microbial translocation was addressed by direct comparison of chimpanzees with a high HCV load and human patients with advanced fibrosis. These data suggest that only in a small minority of HCV patients, hepatic fibrosis corroborates microbial translocation.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Babs E
authors.initials: BE
authors.lastname: Verstrepen
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Ivonne G
authors.initials: IG
authors.lastname: Nieuwenhuis
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Zahra C
authors.initials: ZC
authors.lastname: Fagrouch
authors.affiliation: Division of Pathology and Microbiology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, 3015 CE Rotterdam, The Netherlands.
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D004195:Disease Models, Animal; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics* / Q000382:microbiology / Q000821:virology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D002679:Pan troglodytes; D015854:Up-Regulation
chemical_list: D018950:Lipopolysaccharide Receptors