The Incidence and Significance of Pattern-Recognition Receptors in Chronic Viral Hepatitis Types B and C in Man

Abstract

Chronic viral hepatitis B and C are among the most common and devastating liver diseases worldwide. Immune response plays a crucial role in the course of both diseases. In spite of the importance of the adaptive arm of the immune response, there is a growing role of innate immunity, the earliest confronted with viral attack. Pattern-recognition receptors (PRRs) and, in particular, Toll-like receptors (TLRs) are molecules which are able not only to recognize foreign invaders, but also quickly mount an antiviral defense. Activation of PRRs has been demonstrated in both hepatitis types, i.e. in situ in the liver and on while blood cells. Both viruses, HCV and HBV, are able to subvert the PRR-mediated antiviral response by means of various proteins and enzymes. HCV acts via the non-structural proteins NS2 and NS3/4A, while HBV HBeAg is inversely correlated with TLR activity. Viral counterattack is particularly directed toward dendritic cells, those creating the link with the adaptive immune response. Apart from TLRs, other PRRs such as RIG-1 and MDA-5 are also able to recognize viral infection and participate in the activation of type I interferon synthesis. TLRs manifest gene polymorphism, which was shown to affect several consequences associated with chronic viral hepatitis such as liver cirrhosis and the outcome of liver allotransplantation. There have been numerous attempts to take advantage of the existence and activity of PRRs for the patients' benefit. Several authors examined the role of TLR synthetic agonists as inducers of TLR activation. In hepatitis C the most promising agonists appear to be TLR3, 7, and 9 for potential antiviral therapy. PRRs may also act as potent adjuvants in HBV vaccines. Their baseline mRNA levels may have predictive value in the course of antiviral therapy.

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

“…In the current study, we assessed the effect of iNOS inhibition with small-molecule antagonists or RNAi-mediated gene silencing (knockdown) on human melanoma in the chick chorioallantoic membrane (CAM) model, which has been widely used to study cancer growth and angiogenesis in vivo (18). Our data show that in human melanoma mTOR pathway activation is dependent on iNOS expression/activity, and support a model where iNOS modulates mTOR activity by NO-mediated post-translational modification of the upstream regulator TSC-2.…”

Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Hepatitis C Infection

“…TLRs are predominantly expressed on the cell surface (TLRs1, 2, 4, 5, 6 and 10). However, some TLRs such as TLR3, 7, 8 and 9 are localized in the endosomal compartments (3). Among the mammalian TLRs, three are responsible for recognition of RNA.…”

TLR7 and TLR8 Gene Variations and Susceptibility to Hepatitis C Virus Infection

“…The number of reported genotypic profiles of TLRs is rapidly expanding. However, the number of identified functional TLR polymorphisms remains limited, and parts of some studies have divergent results regarding the significance of polymorphisms and even have contradictory observations [8].…”