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Renal Toll-like receptors: recent advances and implications for disease

Nature Clinical Practice Nephrology volume 2, pages 568–581 (2006)Cite this article

Abstract

Toll-like receptors (TLRs) are proteins that recognize specific molecular patterns of pathogens. They can also interact with a variety of endogenous ligands. When stimulated, TLRs initiate a cascade of signaling events leading to the production of a myriad of cytokines and effector molecules. Early investigations extensively characterized TLRs on cells of the innate immune system. More recently, TLRs have been found to reside in organs such as the heart, lungs, intestines, liver and kidneys. The role of these TLRs is not fully understood and is the subject of intensive current research. The available information indicates that renal TLRs have the potential to interact with exogenous and endogenous ligands, thereby influencing kidney function in health and disease. Here, we present an overview of what is currently known about renal TLRs, and discuss the potential implications for further research and clinical practice.

Key Points

  • Long known to be expressed on cells of the innate immune system, Toll-like receptors (TLRs) have now been localized to mammalian organs, including the kidney

  • TLRs recognize specific molecular patterns of pathogens, and endogenous ligands, and subsequently initiate signaling cascades leading to cytokine production

  • Eleven TLRs have been described; messenger RNA for TLRs 1–10 has been detected in human kidney

  • Data indicate that TLRs have roles in sepsis-induced acute renal failure, ischemic injury, urinary tract infection, rejection of kidney allografts, proteinuria and glomerulonephritis

  • Therapies that target TLRs are being investigated

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Figure 1: Toll-like receptor signaling.
Figure 2: The roles of systemic and renal TLR4 in renal injury.
Figure 3: Renal distribution of TLRs in health and disease.

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Acknowledgements

This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases grant 1RO1 DK60495-01A1 (PCD), a Paul Teschan research fund award (PCD) and a National Kidney Foundation-Indiana grant (TME).

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Authors and Affiliations

  1. Division of Nephrology,

    Tarek M El-Achkar & Pierre C Dagher

  2. Department of Medicine, Indiana University, IN, USA

    Tarek M El-Achkar & Pierre C Dagher

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  1. Tarek M El-Achkar
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  2. Pierre C Dagher
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Correspondence to Pierre C Dagher.

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El-Achkar, T., Dagher, P. Renal Toll-like receptors: recent advances and implications for disease. Nat Rev Nephrol 2, 568–581 (2006). https://doi.org/10.1038/ncpneph0300

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