TLR7 and TLR8 gene variations and susceptibility to hepatitis C virus infection

• Published in: PloS one Vol. 6; no. 10; p. e26235
• Main Authors: Wang, Chiou-Huey, Eng, Hock-Liew, Lin, Kuei-Hsiang, Chang, Cheng-Hsien, Hsieh, Chi-An, Lin, Yen-Li, Lin, Tsun-Mei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.10.2011; Public Library of Science (PLoS)
• Subjects: Adaptive control; Adaptive immunity; Antigens; B cells; Biology; Case-Control Studies; CD14 antigen; Chlamydia; Chromosomes; Control systems; Cytokines; Cytokines - biosynthesis; Dendritic cells; Development and progression; Disease susceptibility; Ethnic Groups - genetics; Female; Females; Gene expression; Gene Expression Regulation; Gene Frequency - genetics; Genes; Genetic aspects; Genetic Predisposition to Disease; Genotypes; Haplotypes; Haplotypes - genetics; Health aspects; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - genetics; Hospitals; Humans; Immune response; Immune system; Immunity; Infection; Infections; Inflammation; Innate immunity; Interferon; Intracellular Space - metabolism; Male; Males; Medical laboratories; Medicine; Middle Aged; mRNA; Polymorphism, Single Nucleotide - genetics; Proteins; Receptors; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; TLR7 protein; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 7 - genetics; Toll-Like Receptor 7 - metabolism; Toll-Like Receptor 8 - agonists; Toll-Like Receptor 8 - genetics; Toll-Like Receptor 8 - metabolism; Toll-like receptors; Viruses; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026235

Toll-like receptors (TLRs) play pivotal roles in the innate immune system and control inflammatory responses and adaptive immunity. We previously evaluated associations between TLR7 and TLR8 gene SNPs and susceptibility to hepatitis C virus (HCV) infection. Our results suggested that TLR7IVS2-151G and TLR8-129G alleles were present at higher frequency in males of an HCV-infected group as compared to a control group (24.1% vs. 14.4%, p = 0.028; 17.6% vs. 6.8%, p = 0.004, respectively). Based upon their recognition of single stranded viral RNA, this suggested that TLR7 and TLR8 played a significant role in anti-HCV immune responses. Here, we studied the functional effects of these polymorphisms by analyzing the mRNA expressions of TLR7 and TLR8 and cytokine production induced ex vivo by TLR7- and TLR8-specific agonists using whole blood of subjects with different genotypes. The percentage of CD14+ cells from those with an AG haplotype that expressed TLR7 and TLR8 was significantly lower, but higher in intensity compared to cells from those with GG and AC haplotypes. Cells from those with an AG haplotype produced more IFN-α and less amounts of pro-inflammatory cytokines upon stimulation. This suggests that variations in TLR7 and TLR8 genes might impair immune responses during HCV infection.