1887

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.

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2016-10-13
2019-10-23
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References

  1. Abad-Fernández M., Vallejo A., Hernández-Novoa B., Díaz L., Gutiérrez C., Madrid N., Muñoz M. A., Moreno S..( 2013;). Correlation between different methods to measure microbial translocation and its association with immune activation in long-term suppressed HIV-1-infected individuals. . J Acquir Immune Defic Syndr 64: 149–153. [CrossRef] [PubMed]
    [Google Scholar]
  2. Balagopal A., Philp F. H., Astemborski J., Block T. M., Mehta A., Long R., Kirk G. D., Mehta S. H., Cox A. L. et al.( 2008;). Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. . Gastroenterology 135: 226–233. [CrossRef]
    [Google Scholar]
  3. Bataller R., Lemon S. M..( 2012;). Fueling fibrosis in chronic hepatitis C. . Proc Natl Acad Sci U S A 109: 14293–14294. [CrossRef] [PubMed]
    [Google Scholar]
  4. Brenchley J. M., Price D. A., Schacker T. W., Asher T. E., Silvestri G., Rao S., Kazzaz Z., Bornstein E., Lambotte O. et al.( 2006;). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. . Nat Med 12: 1365–1371. [CrossRef] [PubMed]
    [Google Scholar]
  5. Brenchley J. M., Paiardini M., Knox K. S., Asher A. I., Cervasi B., Asher T. E., Scheinberg P., Price D. A., Hage C. A. et al.( 2008;). Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. . Blood 112: 2826–2835. [CrossRef] [PubMed]
    [Google Scholar]
  6. Brenchley J. M., Douek D. C..( 2012;). Microbial translocation across the GI tract. . Annu Rev Immunol 30: 149–173. [CrossRef] [PubMed]
    [Google Scholar]
  7. Bukh J..( 2012;). Animal models for the study of hepatitis C virus infection and related liver disease. . Gastroenterol 142: 1279–1287. [CrossRef] [PubMed]
    [Google Scholar]
  8. Dandekar S., George M. D., Bäumler A. J..( 2010;). Th17 cells, HIV and the gut mucosal barrier. . Curr Opin HIV AIDS 5: 173–178. [CrossRef] [PubMed]
    [Google Scholar]
  9. Darling J. M., Aerssens J., Fanning G., McHutchison J. G., Goldstein D. B., Thompson A. J., Shianna K. V., Afdhal N. H., Hudson M. L. et al.( 2011;). Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response. . Hepatol 53: 14–22. [CrossRef] [PubMed]
    [Google Scholar]
  10. Deforges S., Evlashev A., Perret M., Sodoyer M., Pouzol S., Scoazec J. Y., Bonnaud B., Diaz O., Paranhos-Baccalà G. et al.( 2004;). Expression of hepatitis C virus proteins in epithelial intestinal cells in vivo. . J Gen Virol 85: 2515–2523. [CrossRef] [PubMed]
    [Google Scholar]
  11. Dyavar Shetty R., Velu V., Titanji K., Bosinger S. E., Freeman G. J., Silvestri G., Amara R. R..( 2012;). PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques. . J Clin Invest 122: 1712–1716. [CrossRef] [PubMed]
    [Google Scholar]
  12. Favre D., Lederer S., Kanwar B., Ma Z. M., Proll S., Kasakow Z., Mold J., Swainson L., Barbour J. D. et al.( 2009;). Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. . PLoS Pathog 5:,e1000295. [CrossRef] [PubMed]
    [Google Scholar]
  13. French A. L., Evans C. T., Agniel D. M., Cohen M. H., Peters M., Landay A. L., Desai S. N..( 2013;). Microbial translocation and liver disease progression in women coinfected with HIV and hepatitis C virus. . J Infect Dis 208: 679–689. [CrossRef] [PubMed]
    [Google Scholar]
  14. Greenwood E. J., Schmidt F., Kondova I., Niphuis H., Hodara V. L., Clissold L., McLay K., Guerra B., Redrobe S. et al.( 2015;). Simian immunodeficiency virus infection of chimpanzees (Pan troglodytes) shares features of both pathogenic and non-pathogenic lentiviral infections. . PLoS Pathog 11:,e1005146. [CrossRef] [PubMed]
    [Google Scholar]
  15. Houghton M..( 2009;). Discovery of the hepatitis C virus. . Liver Int 29: 82–88. [CrossRef] [PubMed]
    [Google Scholar]
  16. Juompan L. Y., Hutchinson K., Montefiori D. C., Nidtha S., Villinger F., Novembre F. J..( 2008;). Analysis of the immune responses in chimpanzees infected with HIV type 1 isolates. . AIDS Res Hum Retroviruses 24: 573–586. [CrossRef] [PubMed]
    [Google Scholar]
  17. Keele B. F., Jones J. H., Terio K. A., Estes J. D., Rudicell R. S., Wilson M. L., Li Y., Learn G. H., Beasley T. M. et al.( 2009;). Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz. . Nature 460: 515–519. [CrossRef] [PubMed]
    [Google Scholar]
  18. Klatt N. R., Harris L. D., Vinton C. L., Sung H., Briant J. A., Tabb B., Morcock D., McGinty J. W., Lifson J. D. et al.( 2010;). Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection. . Mucosal Immunol 3: 387–398. [CrossRef] [PubMed]
    [Google Scholar]
  19. Kristoff J., Haret-Richter G., Ma D., Ribeiro R. M., Xu C., Cornell E., Stock J. L., He T., Mobley A. D. et al.( 2014;). Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. . J Clin Invest 124: 2802–2806. [CrossRef] [PubMed]
    [Google Scholar]
  20. Lanford R. E., Bigger C., Bassett S., Klimpel G..( 2001;). The chimpanzee model of hepatitis C virus infections. . ILAR J 42: 117–126. [CrossRef] [PubMed]
    [Google Scholar]
  21. Lester R. T., Yao X. D., Ball T. B., McKinnon L. R., Omange W. R., Kaul R., Wachihi C., Jaoko W., Rosenthal K. L., Plummer F. A..( 2009;). HIV-1 RNA dysregulates the natural TLR response to subclinical endotoxemia in Kenyan female sex-workers. . PLoS One 4:,e5644. [CrossRef] [PubMed]
    [Google Scholar]
  22. Marchetti G., Nasta P., Bai F., Gatti F., Bellistrì G. M., Tincati C., Borghi F., Carosi G., Puoti M., Monforte A..( 2012;). Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients. . PLoS One 7:,e32028. [CrossRef] [PubMed]
    [Google Scholar]
  23. Marchetti G., Tincati C., Silvestri G..( 2013;). Microbial translocation in the pathogenesis of HIV infection and AIDS. . Clin Microbiol Rev 26: 2–18. [CrossRef] [PubMed]
    [Google Scholar]
  24. Marchetti G., Cozzi-Lepri A., Tincati C., Calcagno A., Ceccherini-Silberstein F., De Luca A., Antinori A., Castagna A., Puoti M., Monforte A. et al.( 2014;). Immune activation and microbial translocation in liver disease progression in HIV/hepatitis co-infected patients: results from the Icona foundation study. . BMC Infect Dis 14: 79. [CrossRef] [PubMed]
    [Google Scholar]
  25. Márquez M., Romero-Cores P., Montes-Oca M., Martín-Aspas A., Soto-Cárdenas M. J., Guerrero F., Fernández-Gutiérrez C., Girón-González J. A..( 2015;). Immune activation response in chronic HIV-infected patients: influence of Hepatitis C virus coinfection. . PLoS One 10:,e0119568. [CrossRef] [PubMed]
    [Google Scholar]
  26. Mastroianni C. M., Lichtner M., Mascia C., Zuccalà P., Vullo V..( 2014;). Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. . Int J Mol Sci 15: 9184–9208. [CrossRef] [PubMed]
    [Google Scholar]
  27. Mehta G., Gustot T., Mookerjee R. P., Garcia-Pagan J. C., Fallon M. B., Shah V. H., Moreau R., Jalan R..( 2014;). Inflammation and portal hypertension – the undiscovered country. . J Hepatol 61: 155–163. [CrossRef] [PubMed]
    [Google Scholar]
  28. Meuleman P., Steyaert S., Libbrecht L., Couvent S., Van Houtte F., Clinckspoor F., de Hemptinne B., Roskams T., Vanlandschoot P., Leroux-Roels G..( 2006;). Human hepatocytes secrete soluble CD14, a process not directly influenced by HBV and HCV infection. . Clin Chim Acta 366: 156–162. [CrossRef]
    [Google Scholar]
  29. Novembre F. J., Saucier M., Anderson D. C., Klumpp S. A., O'Neil S. P., Brown C. R., Hart C. E., Guenthner P. C., Swenson R. B., McClure H. M..( 1997;). Development of AIDS in a chimpanzee infected with human immunodeficiency virus type 1. . J Virol 71: 4086–4091.[PubMed]
    [Google Scholar]
  30. Pinzone M. R., Celesia B. M., Di Rosa M., Cacopardo B., Nunnari G..( 2012;). Microbial translocation in chronic liver diseases. . Int J Microbiol 2012: 1–12. [CrossRef]
    [Google Scholar]
  31. Prince H. E., Kleinman S., Williams A. E..( 1988;). Soluble IL-2 receptor levels in serum from blood donors seropositive for HIV. . J Immunol 140: 1139–1141.
    [Google Scholar]
  32. Redd A. D., Dabitao D., Bream J. H., Charvat B., Laeyendecker O., Kiwanuka N., Lutalo T., Kigozi G., Tobian A. A. R. et al.( 2009;). Microbial translocation, the innate cytokine response, and HIV-1 disease progression in Africa. . Proc Natl Acad Sci U S A 106: 6718–6723. [CrossRef] [PubMed]
    [Google Scholar]
  33. Rollier C., Drexhage J. A. R., Verstrepen B. E., Verschoor E. J., Bontrop R. E., Koopman G., Heeney J. L..( 2003;). Chronic hepatitis C virus infection established and maintained in chimpanzees independent of dendritic cell impairment. . Hepatology 38: 851–858. [CrossRef] [PubMed]
    [Google Scholar]
  34. Roslansky P. F., Dawson M. E., Novitsky T. J..( 1991;). Plastics, endotoxins, and the Limulus amebocyte lysate test. . J Parenter Sci Technol 45: 83–87.[PubMed]
    [Google Scholar]
  35. Sacchi P., Cima S., Corbella M., Comolli G., Chiesa A., Baldanti F., Klersy C., Novati S., Mulatto P. et al.( 2014;). Liver fibrosis, microbial translocation and immune activation markers in HIV and HCV infections and in HIV/HCV co-infection. . Dig Liver Dis 47: 218–225. [CrossRef] [PubMed]
    [Google Scholar]
  36. Sandler N. G., Koh C., Roque A., Eccleston J. L., Siegel R. B., Demino M., Kleiner D. E., Deeks S. G., Liang T. J. et al.( 2011a;). Host response to translocated microbial products predicts outcomes of patients with hbv or HCV infection. . Gastroenterology 141: 1220–1230. [CrossRef]
    [Google Scholar]
  37. Sandler N. G., Wand H., Roque A., Law M., Nason M. C., Nixon D. E., Pedersen C., Ruxrungtham K., Lewin S. R..Insight Smart Study Group( 2011b;). Plasma levels of soluble CD14 independently predict mortality in HIV infection. . J Infect Dis 203: 780–790. [CrossRef] [PubMed]
    [Google Scholar]
  38. Seki E., Schnabl B..( 2012;). Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut. . J Physiol 590: 447–458. [CrossRef] [PubMed]
    [Google Scholar]
  39. Su G. L., Dorko K., Strom S. C., Nüssler A. K., Wang S. C..( 1999;). CD14 expression and production by human hepatocytes. . J Hepatol 31: 435–442. [CrossRef] [PubMed]
    [Google Scholar]
  40. Verstrepen B. E., de Groot N. G., Groothuismink Z. M., Verschoor E. J., de Groen R. A., Bogers W. M., Janssen H. L., Mooij P., Bontrop R. E. et al.( 2012;). Evaluation of IL-28B polymorphisms and serum IP-10 in hepatitis C infected chimpanzees. . PLoS One 7:,e46645. [CrossRef] [PubMed]
    [Google Scholar]
  41. Walker C. M..( 1997;). Comparative features of hepatitis C virus infection in humans and chimpanzees. . Springer Semin Immunopathol 19: 85–98. [CrossRef] [PubMed]
    [Google Scholar]
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