Hepatic TLR2 & TLR4 expression correlates with hepatic inflammation and TNF-α in HCV & HCV/HIV infection.
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 (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.
Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia. M.Berzsenyi@alfred.org.au
M D
MD
Berzsenyi
S K
SK
Roberts
S
S
Preiss
D J
DJ
Woollard
M R
MR
Beard
N A
NA
Skinner
D S
DS
Bowden
K
K
Visvanathan
D000328:Adult; D060085:Coinfection / Q000276:immunology / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology / Q000473:pathology*; D006526:Hepatitis C / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha