Polymorphisms of Toll-Like Receptors and Their Pathways in Viral Hepatitis

Abstract

Toll-like receptors (TLRs) are an important part of the innate immune response to a variety of pathogens including hepatic viral infections. Activation of TLRs stimulates a complex intracellular signalling cascade that results in production of proinflammatory cytokines and interferons important for antiviral responses as well as induction of the adaptive arm of the immune system. There is substantial evidence for an important role for TLRs and TLR-mediated signalling in the pathogenesis and outcomes of hepatitis B and C in particular, but it might also influence responses to other viral hepatitis infections. Several single nucleotide polymorphisms (SNPs) of TLRs, relevant adaptor molecules and cytokines mediated by TLR signalling have been described that alter innate immune responses and have been implicated in a variety of human diseases including viral and other infections. There is now significant evidence that a number of TLR SNPs can affect various clinical outcomes in Caucasian patients with chronic HCV. However, the role of these polymorphisms in acute and other chronic hepatitis infections, including HBV as well as in non-Caucasian populations, has not been elucidated. In addition, results for SNPs downstream of TLR activation, such as in relevant cytokines, are inconsistent and their influence requires further investigation to determine the clinical significance of genetic variations in these mediators.

Association of Toll‐like receptor 4 polymorphism with hepatitis E virus‐infected Indian patients

“…These are located in the fourth exon and affect the extracellular domain of the molecule, which is associated with receptor hyporesponsiveness but not receptor expression. [15][16][17][18] TLR4 is involved in the pathogenesis of various viral infections [19][20][21][22][23][24] including hepatitis B (HBV) and hepatitis C (HCV) viruses.…”

Functional polymorphisms of TLR8 are associated with hepatitis C virus infection

“…Hepatitis C virus (HCV), a single‐stranded (ss) RNA virus, infects more than 170 million people worldwide . The clinical outcome of HCV infection is highly variable, and genetic factors involving innate immunity are likely to affect disease susceptibility and progression after infection . The role of Toll‐like receptor 8 (TLR8) in host defence against viruses suggests that TLR8 is a suitable marker for exploring the linkage between variants in innate‐immune genes and susceptibility to viral infections.…”

Single Nucleotide Polymorphisms of Toll-Like Receptor 7 and Toll-Like Receptor 9 in Hepatitis C Virus Infection Patients from Central China

“…Several studies have demonstrated an association between TLR7 gene polymorphisms and infection diseases in different populations; however, only one study showed that the TLR7 SNP rs179009 is related to susceptibility to HCV infection in Taiwanese patients in China 17. Most TLR SNPs, except TLR9 SNPs, have been investigated in terms of their relationship with chronic HCV 18. In the present study, we assessed the frequencies of TLR7 (rs179009) and TLR9 (rs187084) SNPs, in order to clarify the role of TLR7, TLR9 polymorphism in HCV infection.…”