Abstract
Liver has a unique vascular system receiving the majority of the blood supply from the gastrointestinal tract through the portal vein and faces continuous exposure to foreign pathogens and commensal bacterial products. These gut-derived antigens stimulate liver cells and result in a distinctive immune response via a family of pattern recognition receptors, the Toll-like receptors (TLRs). TLRs are expressed on Kupffer cells, dendritic cells, hepatic stellate cells, endothelial cells, and hepatocytes in the liver. The crosstalk between gut-derived antigens and TLRs on immune cells trigger a distinctive set of mechanisms to induce immunity, contributing to various acute and chronic liver diseases including liver cirrhosis and hepatocellular carcinoma. Accumulating evidence has shown that TLRs stimulation by foreign antigens induces the production of immunoactivating and immunoregulatory cytokines. Furthermore, the immunoregulatory arm of TLR stimulation can also control excessive tissue damage. With this knowledge at hand, it is important to clarify the dual role of disease-specific TLRs as activators and regulators, especially in the liver. We will review the current understanding of TLR signaling and subsequent immune activation and tolerance by the innate immune system in the liver.
Highlights
The liver faces continuous exposure to many pathogens and commensal bacterial products, and the innate and adaptive immune responses of the liver favor the induction of immunological activation and tolerance as appropriate [1,2,3,4,5]
We recently reported that tumor necrosis factor α (TNFα)-producing CCR9+CD11b+CD11c− macrophages expressed TLR2, TLR4, and TLR6 mRNAs and had a major role in the pathogenesis of acute liver injury in this model by activating Th1 and natural killer T (NKT) cells [25]
The liver is continuously exposed to food antigens and pathogen-associated molecular patterns (PAMPs) from the gastrointestinal tract via the portal vein
Summary
Liver has a unique vascular system receiving the majority of the blood supply from the gastrointestinal tract through the portal vein and faces continuous exposure to foreign pathogens and commensal bacterial products. These gut-derived antigens stimulate liver cells and result in a distinctive immune response via a family of pattern recognition receptors, the Toll-like receptors (TLRs). The immunoregulatory arm of TLR stimulation can control excessive tissue damage With this knowledge at hand, it is important to clarify the dual role of disease-specific TLRs as activators and regulators, especially in the liver.
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