Pattern Recognition Receptors: Significance of Expression in the Liver

Abstract

Pattern recognition receptors (PRRs) are a pivotal part of the immune system. They are distributed in almost every site of higher organisms, able to recognize foreign pathogens or unwanted remnants of metabolism and mount innate immune response. Moreover, PRRs create bridging signaling to initiate adaptive immunity. The liver being the largest organ of the body, exposed to myriads of foreign substances often being immunogenic, is well equipped with PRRs. They act as sentinels of the organ, both in health and disease. In viral hepatitis C at least two of them, RIG-1 and TLR3 sense HCV, induce protective interferon production and create proinflammatory status. The hepatitis B virus is apparently invisible to PRRs, which has recently been denied. Besides, they are active in the course of infection. In liver injury and hepatic fibrogenesis Toll-like receptors (TLRs), predominantly TLR4, TLR3 and TLR9 are associated with gut microflora-related products and DNA from dying hepatocytes, lead to the activation of hepatic stellate cells. The latter initiate production of fibrillar collagens, the main agents forming hepatic fibrosis. Tumor cells of primary liver cancer also express PRRs, mainly TLRs. In concert with non-resolving liver inflammation, they are considered pivotal factors leading to carcinogenesis.

Keywords: Hepatic fibrosis; Hepatitis; Hepatocarcinogenesis; Liver; PRRs; TLRs.

Fig. 1

Hepatitis C. Inhibition of protective immune responses in hepatocyte by viral proteins. dsRNA double-stranded RNA, ssRNA single stranded RNA. Details in the text

Fig. 2

Factors leading to hepatic fibrosis. PDGF platelet-derived growth factor, KC Kupffer cell. Details in the text