Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear Cells From Patients with Chronic Hepatitis C Infection

Abstract

Background: Hepatitis C virus (HCV) is a major cause of chronic liver disease, with around 130 million infected people worldwide. HCV is recognized by Toll-like receptors (TLRs), which are key mediators of innate immune response. Up on activation of TLRs, anti-viral cytokines and pre-inflammatory are produced.

Objectives: In this study, we compared the expression levels of two members of the TLR family (TLR3 and TLR7) that recognize viral RNA in peripheral blood mononuclear cell (PBMC) of patients with chronic HCV infection and healthy controls.

Patients and methods: In this case-control study, blood samples were collected from patients admitted to Blood Transfusion Research Center, Tehran, Iran. PBMC was isolated from blood of chronic HCV patients (n = 25) and age and sex-matched healthy controls (n = 25). RNA was extracted from PBMC and cDNA was synthesized from total RNA templates using reverse transcriptase. The relative level of expression was quantified by real-time PCR using Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and the results were compared by Pfaffl method. Data were analyzed using non-parametric Wilcoxon test. P < 0.05 was considered significant.

Results: In both groups, we had 13 males and 12 females with a mean age of 48.7 ± 16. TLR3 (6.23 ± 0.91 vs. 3.89 ± 0.85, P < 0.001) and TLR7 (1.48 ± 0.82 vs-1.33 ± 1.18, P < 0.001) expressions were significantly lower in patients with chronic HCV infection when compared with healthy controls.

Conclusions: This study suggests that decrease in levels of TLR3 and TLR7 expression is a mechanism that may enable HCV to evade the host innate immune response.

Keywords: Gene Expression; Hepatitis C, Chronic; Immunity, Innate; Toll-Like Receptor 3; Toll-Like Receptor 7.