Journal
JOURNAL OF VIRAL HEPATITIS
Volume 18, Issue 12, Pages 852-860Publisher
WILEY
DOI: 10.1111/j.1365-2893.2010.01390.x
Keywords
HCV; HCV; HIV infection; hepatic inflammation; TLR; TNF-a
Funding
- National Health and Medical Research Council [265603]
- Haemophilia Foundation
- Alfred Hospital [A33332]
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. Signalling activated by Toll-like receptors (TLRs) can result in the production of tumour necrosis factor alpha (TNF-a) 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-a (P = 0.001). A high degree of correlation was seen between hepatic mRNA expression of TNF-avs 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-a mRNA are associated with hepatic inflammation in both HCV and HCV/HIV infection. High correlation between TNF-a and TLR2/TLR4 suggests a role for the innate immune response in TNF-a production. Activation of the innate immune response appears to be independent of infection type.
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