Pattern Recognition Receptors and Liver Failure.

ABSTRACT

Liver failure is a clinical syndrome with many causes, a complicated pathogenesis, diverse clinical manifestations, and very high mortality. No effective treatment is yet available. Main pathological processes of liver failure include direct damage to parenchymal and nonparenchymal liver cells that might be caused by viruses or drugs, immune-mediated indirect damage, inflammation, and ischemia-hypoxia injury that further strengthen liver damage and lead to endotoxemia. Among these causes, viral or bacterial components (called pathogen-associated and damage-associated molecular patterns) are released during tissue damage and cell death and may be recognized by pattern recognition receptors (PRRs) to induce secretion of inflammatory cytokines and chemokines and activate immune cells. This process is an important mechanism that underlies the progression of liver failure. Research concerning the roles of PRR signaling pathways in liver failure is expected to result in development of immunomodulatory drugs to target specific disease stages, immune cells, and signal transduction molecules. This article briefly introduces the research status of six main PRRs (Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, retinoic-acid-inducible gene I-like receptors, cytosolic DNA sensors, C-type lectin receptors, and inflammasomes) in acute liver failure and acute-on-chronic liver failure and explores further research directions.