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Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF‐α in HCV & HCV/HIV infection
Author(s) -
Berzsenyi M. D.,
Roberts S. K.,
Preiss S.,
Woollard D. J.,
Beard M. R.,
Skinner N. A.,
Bowden D. S.,
Visvanathan K.
Publication year - 2011
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2010.01390.x
Subject(s) - tlr2 , hepatitis c virus , immunology , tlr4 , innate immune system , peripheral blood mononuclear cell , hepatitis c , tumor necrosis factor alpha , toll like receptor , inflammation , immune system , medicine , biology , virology , virus , biochemistry , in vitro
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‐α vs 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‐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.