Significance of toll-like receptors 2 and 4 mRNA expression in chronic hepatitis C virus infection

Abstract

Hepatitis C virus (HCV) induces inflammatory signals leading to progressive liver damage. The mechanism of HCV involvement in the host's innate immune responses has not been well characterized and little is known about the molecular mechanisms by which immune cells recognize HCV. In this work we studied Toll-like receptor (TLR) 2 and TLR4, in chronic HCV infection, as recently detected important components of the innate immunity in humans, as microbial recognition receptors. The study involved 30 HCV patients; 15 with chronic hepatitis (group I) and 15 with liver cirrhosis (group II), in addition to 10 healthy controls (group III). mRNA expression of TLR2 and TLR4 in peripheral blood mononuclear cells (PBMCs) was examined using reverse transcriptase PCR. This was carried out in relation to quantitative analysis of HCV-RNA by Real time-PCR and serum tumor necrosis factor-alpha (TNF-alpha) estimation by ELISA. Significant correlation was found, in HCV patients, between the viral load and TLR2 (r = 0.704; p < 0.01 in group I & r = 0.629; p <0.05 in group II) and TLR4 (r = 0.549; p < 0.05 in group I & r = 0.596; p < 0.05 in group II) and between TLR2 and TLR4 (r = 0.814; p < 0.001 in group I & r = 699 p < 0.01 in group II). Over expression of TLR2 and TLR4 was detected in chronic hepatitis patients as compared to controls (p < 0.001). In cirrhotic patients down regulation of TLR4 mRNA expression was found when compared to group I chronic hepatitis (p < 0.001), while TLR2 showed steady over expression. A positive correlation was also detected between TLR2 expression and TNF-alpha in HCV patients (r = 0.571; p < 0.05 in group I & r = 0.723; p < 0.01 in group II), while a weak relationship was found between TLR4 and TNF-alpha in cirrhotic patients. (r = 0.359; p > 0.05). TLR2 correlated significantly with the hepatic necroinflammatory activity grade (r = 0.629; p < 0.05 in group I & r 0.502; p < 0.05 in group II), while TLR4 correlated with the fibrosis stage (r = 0.682; p < 0.01). On the other hand no correlation could be detected between TLR2 and TLR4 and the child's grade in cirrhotic patients. It is concluded that TLR2 and TLR4 may play a vital role in HCV recognition, initiation and progression of HCV induced liver diseases. Lager scale studies as well as advanced molecular researches on immune-modulation of TLRs are recommended. This may have the way to a new therapeutic tool for HCV.