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Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-α in HCV & HCV/HIV infection

  1. M. D. Berzsenyi1,
  2. S. K. Roberts1,
  3. S. Preiss2,
  4. D. J. Woollard3,
  5. M. R. Beard4,5,
  6. N. A. Skinner6,
  7. D. S. Bowden2,
  8. K. Visvanathan6

Article first published online: 3 NOV 2010

DOI: 10.1111/j.1365-2893.2010.01390.x

Issue

Journal of Viral Hepatitis

Journal of Viral Hepatitis

Volume 18, Issue 12, pages 852–860, December 2011

Additional Information

How to Cite

Berzsenyi, M. D., Roberts, S. K., Preiss, S., Woollard, D. J., Beard, M. R., Skinner, N. A., Bowden, D. S. and Visvanathan, K. (2011), Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-α in HCV & HCV/HIV infection. Journal of Viral Hepatitis, 18: 852–860. doi: 10.1111/j.1365-2893.2010.01390.x

Author Information

  1. 1

    Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia

  2. 2

    Molecular Microbiology and Research & Molecular Development Laboratories, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia

  3. 3

    Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia

  4. 4

    Infectious Diseases Laboratories Institute of Medical and Veterinary Science, Adelaide, South Australia

  5. 5

    School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia

  6. 6

    Innate Immunity Laboratory, Monash Institute of Medical Research, Monash Medical Centre, Clayton, Victoria, Australia

*Dr. Mark D. Berzsenyi, Department of Gastroenterology, Alfred Hospital, Prahran 3181, Victoria, Australia. E-mail: M.Berzsenyi@alfred.org.au

Publication History

  1. Issue published online: 18 NOV 2011
  2. Article first published online: 3 NOV 2010
  3. Received June 2010; accepted for publication September 2010

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Keywords:

  • HCV;
  • HCV/HIV infection;
  • hepatic inflammation;
  • TLR;
  • TNF-α

Summary.  Signalling activated by Toll-like receptors (TLRs) can result in the production of tumour necrosis factor alpha (TNF-α) which is implicated in hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection. No study has examined or compared hepatic expression of TLRs in both HCV and HCV/HIV. Liver and peripheral blood mononuclear cells (PBMCs) were obtained from HCV & HCV/HIV-infected patients and PBMCs from HIV-infected patients. Liver RNA was analysed by microarray and reverse transcription quantitative PCR (RT-qPCR). PBMCs were analysed by flow cytometry. Associations with hepatic histology and infection type were sought. Forty-six HCV, 20 HIV and 27 HCV/HIV-infected patients were recruited. Increasing Metavir inflammatory activity score was associated with increased hepatic TLR mRNA by RT-qPCR: TLR2 (P ≤ 0.001), TLR4 (P = 0.008) and TNF-α (P ≤ 0.001). A high degree of correlation was seen between hepatic mRNA expression of TNF-αvs TLR2 (r2 = 0.66, P < 0.0001) and TLR4 (r2 = 0.60, P < 0.0001). No differences in TLR gene or protein expression was observed between HCV, HCV/HIV- or HIV-infected groups. Hepatic TLR2, TLR4 and TNF-α mRNA are associated with hepatic inflammation in both HCV and HCV/HIV infection. High correlation between TNF-α and TLR2/TLR4 suggests a role for the innate immune response in TNF-α production. Activation of the innate immune response appears to be independent of infection type.

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