Downregulation of Human Toll-like Receptor 2 and 4 Genes in Inactive Carriers of Hepatitis B Virus Infection-A Possible Mode of Viral Persistence

Abstract

AIM: Toll-like receptors (TLRs) although comprise an integral part of innate immune defense mechanism, role of TLRs in hepatitis B virus (HBV) mediated disease categories are sparsely studied.The aim of the present study was to assess host TLR2 and TLR4 gene expressions in various stages of HBV infection in relation to viral replication intermediate pregenomic RNA (pgRNA) in peripheral blood mononuclear cells (PBMCs) and HBV DNA concentration in sera. METHODS: TLR2 and TLR4 mRNA expression in conjunction with PgRNA level in PBMCs of 65 treatment naïve HBV infected patients grouped in to acute (AHB), inactive carriers (IC), liver cirrhosis (Cirr) and hepatocellular carcinoma (HCC) were evaluated by reverse transcription polymerase chain reaction (RT-PCR) assay. Serum HBV DNA was measured by real time PCR assay. Thirty voluntary blood donors served as controls RESULTS: Compared to controls, TLR2 gene expression was significantly reduced in AHB (p=0.003), IC(p=0.006) and Cirr(p=0.01) while expression of TLR4 gene was significantly abridged in IC (p=0.0005) group only. A significantly higher elevation in the expression of TLR4 was noted in HCC (p=0.0001). Despite having lower level of HBV DNA, ICs had substantial echelon of pgRNA comparable to other groups. CONCLUSION: The results showed differential expression of TLR2 and TLR4 mRNA in HBV disease categories. On top, significant downregulation of both TLR2 and TLR4 expression was encountered in ICs only. This observation alongwith the level of viral pgRNA in ICs may well be indicative of dysregulation of one of the crucial arm of innate immune mechanism favoring long term persistence of the virus towards a chronic infection.