Publications & Reports

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

Berzsenyi MD, Roberts SK, Preiss S, Woollard DJ, Beard MR, Skinner NA, Bowden DS, Visvanathan K
Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia Molecular Microbiology and Research & Molecular Development Laboratories, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia Macfarlane Bur

Abstract

Summary. Signalling activated by Toll-like receptors (TLRs) can result in the production of tumour necrosis factor alpha (TNF-alpha) 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-alpha (P </= 0.001). A high degree of correlation was seen between hepatic mRNA expression of TNF-alphavs TLR2 (r(2) = 0.66, P < 0.0001) and TLR4 (r(2) = 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-alpha mRNA are associated with hepatic inflammation in both HCV and HCV/HIV infection. High correlation between TNF-alpha and TLR2/TLR4 suggests a role for the innate immune response in TNF-alpha production. Activation of the innate immune response appears to be independent of infection type.

Publication

  • Journal: Journal of Viral Hepatitis
  • Published: 01/12/2011
  • Volume: 18
  • Issue: 12
  • Pagination: 852-860