Association of the Polymorphism of the Toll-like Receptor (TLR) 3 and TLR9 Genes with Hepatitis C Virus-Specific Cell-Mediated Immunity Outcomes Among Egyptian Healthcare Workers.

Variations in the immune response could explain resistance to hepatitis C virus (HCV) infection. Toll-like receptor gene (TLR)-3 is an innate detector of dsRNA viruses, and the TLR9 gene recognizes bacterial and viral unmethylated CpG motifs. We previously reported that TLR3.rs3775290 CC genotype was associated with HCV chronicity and that the TLR9 gene played no major role in this infection. This study identified the role of TLR3.rs3775290 (c.1377C/T), TLR9.rs5743836 (-1237T→C) and TLR9.rs352140 (G2848A) gene polymorphisms in predicting the outcome of HCV-specific cell-mediated immunity (CMI) among Egyptian healthcare workers (HCWs). We enrolled 265 HCWs in this study and divided them into four groups. Group1: 140 seronegative-aviraemic HCWs; group2: 20 seronegative-viraemic HCWs; group3: 35 subjects with spontaneously resolved HCV infection; and group4: 70 chronic HCV HCWs (patients). All subjects were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis for the TLR3.rs3775290, TLR9.rs5743836 and TLR9.rs352140 single nucleotide polymorphisms (SNPs). We, also, quantified HCV-specific CMI in the four groups using an interferon gamma (IFN-γ) enzyme-linked immunospot (ELISpot) assay in response to nine HCV genotype4a, overlapping 15mer peptide pools covering the whole viral genome. No statistically significant difference was found between CMI responding subjects with different HCV states and TLR3.rs3775290 or TLR9.rs352140 genotypes. However, there was a significant relationship between the outcome of the HCV-specific CMI and the TLR9.rs5743836 genotype among the responding subjects (p=0.005) and the chronic HCV patients (p=0.044). In conclusion, TLR9.rs5743836 SNP, but not TLR3.rs3775290 or TLR9.rs352140 genotypes, could predict the outcome of HCV-specific CMI responses among Egyptians infected with genotype-4.