Pattern Recognition Receptors: Significance of Expression in the Liver
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(2020) 68:29
REVIEW
Pattern Recognition Receptors: Significance of Expression in the Liver Jan Żeromski1 · Agata Kierepa2 · Bartosz Brzezicha1 · Arleta Kowala‑Piaskowska2 · Iwona Mozer‑Lisewska2 Received: 31 December 2019 / Accepted: 2 September 2020 © The Author(s) 2020
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 PRRs · TLRs · Liver · Hepatitis · Hepatic fibrosis · Hepatocarcinogenesis Abbreviations PRR Pattern recognition receptor RIG-1 Retinoic acid-inducible gene 1 TLR Toll-like receptor PAMP Pathogen-associated molecular pattern DAMP Danger-associated molecular pattern NF-κB Nuclear factor kappa (light-chain-enhancer of activated B cells) AP Activator protein IRF Interferon regulatory factor MHC Major histocompatibility complex HSC Hepatic stellate cell NLR NOD-like receptor TRIF TIR-domain-containing adapter-inducing interferon-β CpG-ODN CpG oligodeoxynucleotide
* Jan Żeromski [email protected] 1
Chair of Pathomorphology and Clinical Immunology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland
Chair and Department of Infectious Diseases, Hepatology and Acquired Immunodeficiencies, Karol Marcinkowski University of Medical Sciences, Poznan, Poland
2
pDC Plasmacytoid dendritic cell PBMC Peripheral blood mononuclear cell NK Natural killer cell Treg Regulatory T cell Th17 T helper 17 cell HCC Hepatocellular carcinoma MDA5 Melanoma differentiation-associated protein 5 IPS-1 Interferon-beta promoter stimulator 1 SNP Single nucleotide polymorphism NOD2 Nucleotide-binding oligomerization domain containing 2 MD2 Myeloid differentiation protein 2 Tak1Hep TGFβ-activated kinase 1
Introduction Pattern recognition receptors (PRRs) are evolutionally very old, germ line encoded receptors express
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