Toll-like receptors in pathophysiology of liver diseases

Abstract

Toll-like receptors (TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte (i.e., hepatocellular injury and regeneration) or hepatic stellate cell (i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases.

Keywords: Toll-like receptors; Innate immunity; Liver disease; Pathophysiology; Signaling

Core tip: Toll-like receptors (TLRs) are known to be pattern recognition receptors that recognize pathogen- and damage-associated molecular pattern molecules and thus participate in the activation of innate immune system. TLR signaling plays a significant role in liver diseases, whereas inflammatory or immune pathologies targeting distinct liver cells are based on complex immune responses. Herein, we review the current data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases.