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Toll-like Receptors in Inflammation pp 125–142Cite as

Toll-like receptor signaling in the liver

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Part of the book series: Progress in Inflammation Research ((PIR))

Conclusion

TLR-mediated innate immune responses are indispensable for the host defense against microbial infection. Through its anatomical links with the intestine the liver is the main target of gut-derived bacteria and bacterial products. The liver not only serves as first line of defense against bacteria and endotoxin, but also plays a major role in eliminating endotoxin from the body. Hepatic cell populations possess mechanisms that limit the response to bacterial products, such as the low expression of CD14 and TLR4, to prevent inflammation due to the constant exposure to gut-derived endotoxin. When this balance is disrupted and endotoxin levels exceed threshold levels as seen during microbial infection, ethanol-induced loss of intestinal barrier function or loss of functional liver mass, TLRs on several hepatic cell populations mediate proinflammatory and pro-proliferative responses which are at the center of the pathophysiology of these diseases. TLRs also seem to be involved in the pathology of chronic HCV infection by downregulating the innate immune response in early phases and inducing inflammation in later stages of the disease. There is still a fundamental lack of knowledge about the functional expression of TLR and TLR adapter molecules in the liver under normal and pathological conditions. Future studies need to further investigate (1) the role of TLRs in hepatic fibrogenesis and (2) characterize the “good” signals induced by TLR, i.e., as enhanced immune response, protection from apoptosis and proliferation, versus the “bad” signals such as hepatotoxicity and chronic inflammation. Further understanding of the TLR signaling pathways in the liver will help to shape new concepts with TLRs and their downstream mediators as pharmacological targets in liver disease.

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Authors and Affiliations

  1. Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, 10026, USA

    Ekihiro Seki, David A. Brenner & Robert F. Schwabe

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  1. Ekihiro Seki
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  2. David A. Brenner
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  1. Cytokine Research Group, Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland

    Luke A.J. O’Neill  & Elizabeth Brint  & 

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Seki, E., Brenner, D.A., Schwabe, R.F. (2006). Toll-like receptor signaling in the liver. In: O’Neill, L.A., Brint, E. (eds) Toll-like Receptors in Inflammation. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7441-1_7

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