Toll‐like receptors in hepatitis C infection: Implications for pathogenesis and treatment

Abstract

Hepatitis C virus (HCV) infection is a significant global health problem, affecting over 150 million people worldwide. While the critical role of the adaptive immune system in HCV infection is well-established, the importance of the innate immune system in HCV infection has only been recognized in more recent years. Toll-like receptors form the cornerstone of the innate immune response, and there is considerable evidence for their crucial role in hepatitis C infection. This review outlines recent advances made in our understanding of the role of Toll-like receptor function in HCV infection, exploring how HCV manipulates host immunity to evade immune clearance and establish persistent infection despite leading to inflammatory hepatic damage.

Sex-specific effects of TLR9 promoter variants on spontaneous clearance of HCV infection

“…The mechanism by which TLR9 contributes to antiviral signalling during HCV infection remains poorly understood. It has been proposed that pDCs can be activated via TLR9 through the HCV RNA polyuridine tail,13 although this awaits further confirmation and would be informative to verify in liver cells which also express TLR9 7 8. In any case, it appears plausible that modulation of TLR9 mRNA levels may enhance or suppress the functionality of any directly TLR9-dependent response to HCV components or possibly endogenously generated Damage-associated molecular pattern molecules (eg, high-mobility group protein 1 DNA complexes50) released during the infectious cycle.…”

“…Other studies showed inhibitory effects of HCV particles on pDC-associated IFN alpha production in response to TLR9 activation 12. Furthermore, antiviral effects were determined in HCV-infected patients upon stimulation of TLR9 13. However, the importance of TLR9 in a setting of natural HCV infection has not been demonstrated.…”

Single-nucleotide polymorphism of Toll-like receptor 4 and interleukin-10 in response to interferon-based therapy in Egyptian chronic hepatitis C patients

“…While the critical role of the adaptive immune system in HCV infection is well established, the importance of the innate immune system in HCV infection has only been recognized in recent years. Toll-like receptors (TLRs) form the cornerstone of the innate immune response, and there is a considerable evidence for their crucial role in HCV infection [1]. TLRs are a family of transmembrane pattern-recognition receptors (PRR) that play a key role in innate and adaptive immunity by recognizing structural components unique to bacteria, fungi and viruses [18].…”

“…There are approximately 10 functional TLRs identified in humans, recognizing a wide range of microbial ligands [1,19]. Each receptor has two domains: an extracellular leucine-rich receptor (LRR) domain and an intracellular Toll-interleukin (IL-1) receptor (TIR) domain [20].…”

“…Hepatitis C virus (HCV) is a significant global health problem, affecting over 180 million people worldwide [1], and it is a leading cause in cirrhosis and liver cancer. The Egyptian Demographic Health Survey (EDHS), a crosssectional survey conducted in 2008, estimated the HCV prevalence in the 15-to 59-year-old age group to be 14.7 % [2].…”