Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Pattern recognition receptors and the inflammasome in kidney disease

Nature Reviews Nephrology volume 10, pages 398–414 (2014)Cite this article

Subjects

Key Points

  • Toll-like receptors (TLRs), nucleotide-binding oligomerization domain receptors (NLRs) and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome regulate inflammatory and repair processes in the kidneys

  • TLRs prevent invasion and growth of pathogens in the urinary tract

  • Inappropriate activation of TLRs, NLRs and the NLRP3 inflammasome is a major cause of acute and chronic kidney disease

  • Gene-association studies have revealed connections between TLR gene mutations and the development of several inflammatory kidney disorders

  • TLRs, NLRs and the NLRP3 inflammasome represent attractive novel drug targets to prevent and intervene in kidney inflammation and suppress immunopathology in kidney disease

Abstract

Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain receptors (NLRs) are families of pattern recognition receptors that, together with inflammasomes, sense and respond to highly conserved pathogen motifs and endogenous molecules released upon cell damage or stress. Evidence suggests that TLRs, NLRs and the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome have important roles in kidney diseases through regulation of inflammatory and tissue-repair responses to infection and injury. In this Review, we discuss the pathological mechanisms that are related to TLRs, NLRs and NLRP3 in various kidney diseases. In general, these receptors are protective in the host defence against urinary tract infection, but can sustain and self-perpetuate tissue damage in sterile inflammatory and immune-mediated kidney diseases. TLRs, NLRs and NLRP3, therefore, have become promising drug targets to enable specific modulation of kidney inflammation and suppression of immunopathology in kidney disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Roles of TLRs, NLRs and the NLRP3 inflammasome in renal tissue repair and remodelling and renal diseases.
Figure 2: Pathophysiological role of TLRs, NLRs and the NLRP3 inflammasome in various renal disorders.
Figure 3: TLRs, NLRs and the NLRP3 inflammasome drive host defence and tissue repair mechanisms by the clearance of pathogens and cell debris and by regulation of repair pathways.

Similar content being viewed by others

References

  1. Creagh, E. M. & O'Neill, L. A. TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol. 27, 352–357 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805–820 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. Leemans, J. C., Cassel, S. L. & Sutterwala, F. S. Sensing damage by the NLRP3 inflammasome. Immunol. Rev. 243, 152–162 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bryant, C. E. & Monie, T. P. Mice, men and the relatives: cross-species studies underpin innate immunity. Open Biol. 2, 120015 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anders, H. J. Toll-like receptors and danger signaling in kidney injury. J. Am. Soc. Nephrol. 21, 1270–1274 (2010).

    Article  CAS  PubMed  Google Scholar 

  6. Beutler, B. Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases. Immunol. Rev. 227, 248–263 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kawai, T. & Akira, S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat. Immunol. 11, 373–384 (2010).

    Article  CAS  PubMed  Google Scholar 

  8. Watters, T. M., Kenny, E. F. & O'Neill, L. Structure, function and regulation of the Toll/IL-1 receptor adaptor proteins. Immunol. Cell Biol. 85, 411–419 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. O'Neill, L. A. & Bowie, A. G. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat. Rev. Immunol. 7, 353–364 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Ye, Z. & Ting, J. P. NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr. Opin. Immunol. 20, 3–9 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Carneiro, L. A., Magalhaes, J. G., Tattoli, I., Philpott, D. J. & Travassos, L. H. Nod-like proteins in inflammation and disease. J. Pathol. 214, 136–148 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Latz, E., Xiao, T. S. & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397–411 (2013).

    Article  CAS  PubMed  Google Scholar 

  13. Wen, H., Miao, E. A. & Ting, J. P.-Y. Mechanisms of NOD-like receptor-associated inflammasome activation. Immunity 39, 432–441 (2013).

    Article  CAS  PubMed  Google Scholar 

  14. Anders, H. J. & Muruve, D. A. The inflammasomes in kidney disease. J. Am. Soc. Nephrol. 22, 1007–1018 (2011).

    Article  CAS  PubMed  Google Scholar 

  15. Iyer, S. S. et al. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity 39, 311–323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Nakahira, K. et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 12, 222–230 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Shimada, K. et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity 36, 401–414 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Lorenz, G., Darisipudi, M. N. & Anders, H.-J. Canonical and non-canonical effects of the NLRP3 inflammasome in kidney inflammation and fibrosis. Nephrol. Dial. Transplant. 41–48 (2013).

  21. Ragnarsdóttir, B., Lutay, N., Gronberg-Hernandez, J., Köves, B. & Svanborg, C. Genetics of innate immunity and UTI susceptibility. Nat. Rev. Urol. 8, 449–468 (2011).

    Article  PubMed  Google Scholar 

  22. Fischer, H., Yamamoto, M., Akira, S., Beutler, B. & Svanborg, C. Mechanism of pathogen-specific TLR4 activation in the mucosa: fimbriae, recognition receptors and adaptor protein selection. Eur. J. Immunol. 36, 267–277 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Hagberg, L. et al. Difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and difference in susceptibility to gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect. Immun. 46, 839–844 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hagberg, L., Briles, D. E. & Edén, C. S. Evidence for separate genetic defects in C3H/HeJ and C3HeB/FeJ mice, that affect susceptibility to gram-negative infections. J. Immunol. 134, 4118–4122 (1985).

    CAS  PubMed  Google Scholar 

  25. Agace, W., Hedges, S. & Svanborg, C. Lps genotype in the C57 black mouse background and its influence on the interleukin-6 response to E. coli urinary tract infection. Scand. J. Immunol. 35, 531–538 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Leemans, J. C. et al. The toll interleukin-1 receptor (IL-1R) 8/single Ig domain IL-1R-related molecule modulates the renal response to bacterial infection. Infect. Immun. 80, 3812–3820 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schilling, J. D., Martin, S. M., Hung., C. S., Lorenz, R. G. & Hultgren, S. J. Toll-like receptor 4 on stromal and hematopoietic cells mediates innate resistance to uropathogenic Escherichia coli. Proc. Natl Acad. Sci. USA 100, 4203–4208 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Patole, P. S. et al. Toll-like receptor-4: renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis. Kidney Int. 68, 2582–2587 (2005).

    Article  CAS  PubMed  Google Scholar 

  29. Tsuboi, N. et al. Roles of toll-like receptors in C-C chemokine production by renal tubular epithelial cells. J. Immunol. 169, 2026–2033 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Chassin, C. et al. Renal collecting duct epithelial cells react to pyelonephritis-associated Escherichia coli by activating distinct TLR4-dependent and -independent inflammatory pathways. J. Immunol. 177, 4773–4784 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Good, D. W., George, T. & Watts, B. A. Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes. Am. J. Physiol. Ren. Physiol. 297, F866–F874 (2009).

    Article  CAS  Google Scholar 

  32. Good, D. W., George, T. & Watts, B. A. Toll-like receptor 2 mediates inhibition of HCO3− absorption by bacterial lipoprotein in medullary thick ascending limb. Am. J. Physiol. Renal Physiol. 299, F536–F544 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chassin, C. et al. TLR4 facilitates translocation of bacteria across renal collecting duct cells. J. Am. Soc. Nephrol. 19, 2364–2374 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ragnarsdóttir, B. et al. Reduced toll-like receptor 4 expression in children with asymptomatic bacteriuria. J. Infect. Dis. 196, 475–484 (2007).

    Article  CAS  PubMed  Google Scholar 

  35. Yin, X. et al. Association of Toll-like receptor 4 gene polymorphism and expression with urinary tract infection types in adults. PLoS ONE 5, e14223 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ragnarsdóttir, B. et al. Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection. PLoS ONE 5, e10734 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karoly, E. et al. Heat shock protein 72 (HSPA1B) gene polymorphism and Toll-like receptor (TLR) 4 mutation are associated with increased risk of urinary tract infection in children. Pediatr. Res. 61, 371–374 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Hawn, T. R. et al. Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLoS ONE 4, e5990 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kau, A. L. et al. Enterococcus faecalis tropism for the kidneys in the urinary tract of C57BL/6J mice. Infect. Immun. 73, 2461–2468 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yang, C.-W. et al. Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells. Kidney Int. 69, 815–822 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Tabel, Y., Berdeli, A. & Mir, S. Association of TLR2 gene Arg753Gln polymorphism with urinary tract infection in children. Int. J. Immunogenet. 34, 399–405 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Hawn, T. R. et al. Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women. PLoS ONE 4, e8300 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Cheng, C.-H., Lee, Y.-S., Chang, C.-J. & Lin, T.-Y. Genetic polymorphisms in Toll-like receptors among pediatric patients with renal parenchymal infections of different clinical severities. PLoS ONE 8, e58687 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cheng, C.-H., Lee, Y.-S., Tsau, Y.-K. & Lin, T.-Y. Genetic polymorphisms and susceptibility to parenchymal renal infection among pediatric patients. Pediatr. Infect. Dis. J. 30, 309–314 (2011).

    Article  PubMed  Google Scholar 

  45. Andersen-Nissen, E. et al. Cutting edge: Tlr5−/− mice are more susceptible to Escherichia coli urinary tract infection. J. Immunol. 178, 4717–4720 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Zhang, D. et al. A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303, 1522–1526 (2004).

    Article  CAS  PubMed  Google Scholar 

  47. Devarajan, P. Update on mechanisms of ischemic acute kidney injury. J. Am. Soc. Nephrol. 17, 1503–1520 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Chvojka, J. et al. New developments in septic acute kidney injury. Physiol. Res. 59, 859–869 (2010).

    CAS  PubMed  Google Scholar 

  49. Miller, R. P., Tadagavadi, R. K., Ramesh, G. & Reeves, W. B. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2, 2490–518 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Lech, M. et al. Macrophage phenotype controls long-term AKI outcomes—kidney regeneration versus atrophy. J. Am. Soc. Nephrol. 25, 292–304 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gonçalves, G. M., Castoldi, A., Braga, T. T. & Câmara, N. O. S. New roles for innate immune response in acute and chronic kidney injuries. Scand. J. Immunol. 73, 428–435 (2011).

    Article  CAS  PubMed  Google Scholar 

  52. Bonventre, J. V. & Zuk, A. Ischemic acute renal failure: an inflammatory disease? Kidney Int. 66, 480–485 (2004).

    Article  CAS  PubMed  Google Scholar 

  53. Mkaddem, S. B. et al. Heat shock protein gp96 interacts with protein phosphatase 5 and controls toll-like receptor 2 (TLR2)-mediated activation of extracellular signal-regulated kinase (ERK) 1/2 in post-hypoxic kidney cells. J. Biol. Chem. 284, 12541–12549 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wu, H. et al. HMGB1 contributes to kidney ischemia reperfusion injury. J. Am. Soc. Nephrol. 21, 1878–1890 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Dessing, M. C. et al. RAGE does not contribute to renal injury and damage upon ischemia/reperfusion-induced injury. J. Innate. Immun. 4, 80–85 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Wu, H. et al. TLR4 activation mediates kidney ischemia/reperfusion injury. J. Clin. Invest. 117, 2847–2859 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Allam, R. et al. Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4. J. Am. Soc. Nephrol. 23, 1375–1388 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shah, N. et al. Prevention of acute kidney injury in a rodent model of cirrhosis following selective gut decontamination is associated with reduced renal TLR4 expression. J. Hepatol. 56, 1047–1053 (2012).

    Article  CAS  PubMed  Google Scholar 

  59. Wolfs, T. G. A. M. et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-γ and TNF-α mediated up-regulation during inflammation. J. Immunol. 168, 1286–1293 (2002).

    Article  CAS  PubMed  Google Scholar 

  60. Leemans, J. C. et al. Renal-associated TLR2 mediates ischemia/reperfusion injury in the kidney. J. Clin. Invest. 115, 2894–2903 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Pulskens, W. P. et al. Toll-like receptor-4 coordinates the innate immune response of the kidney to renal ischemia/reperfusion injury. PLoS ONE 3, e3596 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chen, J. et al. Toll-like receptor 4 regulates early endothelial activation during ischemic acute kidney injury. Kidney Int. 79, 288–299 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Rusai, K. et al. Toll-like receptors 2 and 4 in renal ischemia/reperfusion injury. Pediatr. Nephrol. 25, 853–860 (2010).

    Article  PubMed  Google Scholar 

  64. Shigeoka, A. A. et al. TLR2 is constitutively expressed within the kidney and participates in ischemic renal injury through both MyD88-dependent and -independent pathways. J. Immunol. 178, 6252–6258 (2007).

    Article  CAS  PubMed  Google Scholar 

  65. Fukuzawa, N., Petro, M., Baldwin, W. M., Gudkov, A. V. & Fairchild, R. L. A TLR5 agonist inhibits acute renal ischemic failure. J. Immunol. 187, 3831–3839 (2011).

    Article  CAS  PubMed  Google Scholar 

  66. Li, X. et al. The role of Toll-like receptor (TLR) 2 and 9 in renal ischemia and reperfusion injury. Urology 81, 1379.e15–1379.e20 (2013).

    Google Scholar 

  67. Shigeoka, A. A. et al. Nod1 and nod2 are expressed in human and murine renal tubular epithelial cells and participate in renal ischemia reperfusion injury. J. Immunol. 184, 2297–2304 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Iyer, S. S. et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc. Natl Acad. Sci. USA 106, 20388–20393 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Shigeoka, A. A. et al. An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. J. Immunol. 185, 6277–85 (2010).

    Article  CAS  PubMed  Google Scholar 

  70. Kim, H. J. et al. NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury. J. Pharmacol. Exp. Ther. 346, 465–472 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Melnikov, V. Y. et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J. Clin. Invest. 107, 1145–1152 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Farrar, C. A. et al. Inhibition of TLR2 promotes graft function in a murine model of renal transplant ischemia-reperfusion injury. FASEB J. 26, 799–807 (2012).

    Article  CAS  PubMed  Google Scholar 

  73. Andrade-Oliveira, V. et al. TLR4 mRNA levels as tools to estimate risk for early posttransplantation kidney graft dysfunction. Transplantation 94, 589–595 (2012).

    Article  PubMed  Google Scholar 

  74. Krüger, B. et al. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc. Natl Acad. Sci. USA 106, 3390–3395 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Krüger, B. et al. A comprehensive genotype-phenotype interaction of different Toll-like receptor variations in a renal transplant cohort. Clin. Sci. (Lond.). 119, 535–544 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Wu, H. et al. Absence of MyD88 signaling induces donor-specific kidney allograft tolerance. J. Am. Soc. Nephrol. 23, 1701–1716 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Dessing, M. C. et al. Intragraft Toll-like receptor profiling in acute renal allograft rejection. Nephrol. Dial. Transplant. 25, 4087–4092 (2010).

    Article  CAS  PubMed  Google Scholar 

  78. Ducloux, D. et al. Relevance of Toll-like receptor-4 polymorphisms in renal transplantation. Kidney Int. 67, 2454–2461 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Fekete, A. et al. Association between heat shock protein 70s and toll-like receptor polymorphisms with long-term renal allograft survival. Transplant. Int. 19, 190–196 (2006).

    Article  CAS  Google Scholar 

  80. Palmer, S. M. et al. Donor polymorphisms in Toll-like receptor-4 influence the development of rejection after renal transplantation. Clin. Transplant. 20, 30–36 (2005).

    Article  Google Scholar 

  81. Nogueira, E. et al. Incidence of donor and recipient toll-like receptor-4 polymorphisms in kidney transplantation. Transplant. Proc. 39, 412–414 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Eikmans, M. et al. The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome. Transplantation 94, 478–485 (2012).

    Article  CAS  PubMed  Google Scholar 

  83. Cervera, C. et al. The influence of innate immunity gene receptors polymorphisms in renal transplant infections. Transplantation 83, 1493–1500 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Martins, G. A., Kawamura, M. T. & Carvalho, M. G. Detection of DNA in the plasma of septic patients. Ann. NY Acad. Sci. 906, 134–140 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Zhang, Q., Itagaki, K. & Hauser, C. J. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase. Shock 34, 55–59 (2010).

    Article  CAS  PubMed  Google Scholar 

  86. Wang, H., Yang, H. & Tracey, K. J. Extracellular role of HMGB1 in inflammation and sepsis. J. Intern. Med. 255, 320–331 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. El-Achkar, T. M. & Dagher, P. C. Renal Toll-like receptors: recent advances and implications for disease. Nat. Clin. Pract. Nephrol. 2, 568–581 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. El-Achkar, T. M. et al. Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney. Am. J. Physiol. Renal Physiol. 290, F1034–F1043 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Dear, J. W. et al. Sepsis-induced organ failure is mediated by different pathways in the kidney and liver: acute renal failure is dependent on MyD88 but not renal cell apoptosis. Kidney Int. 69, 832–836 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Castoldi, A. et al. TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis. PLoS ONE 7, e37584 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Cunningham, P. N., Wang, Y., Guo, R., He, G. & Quigg, R. J. Role of Toll-like receptor 4 in endotoxin-induced acute renal failure. J. Immunol. 172, 2629–2635 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Yasuda, H. et al. Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury. Am. J. Physiol. Renal Physiol. 294, F1050–F1058 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Scott, A. M. & Saleh, M. The inflammatory caspases: guardians against infections and sepsis. Cell Death Differ. 14, 23–31 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Brenmoehl, J. et al. Genetic variants in the NOD2/CARD15 gene are associated with early mortality in sepsis patients. Intensive Care Med. 33, 1541–1548 (2007).

    Article  CAS  PubMed  Google Scholar 

  95. Stroo, I. et al. Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease. Biol. Open 1, 1239–1247 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Zhang, B., Ramesh, G., Uematsu, S., Akira, S. & Reeves, W. B. TLR4 signaling mediates inflammation and tissue injury in nephrotoxicity. J. Am. Soc. Nephrol. 19, 923–932 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Sallustio, F. et al. Human renal stem/progenitor cells repair tubular epithelial cell injury through TLR2-driven inhibin-A and microvesicle-shuttled decorin. Kidney Int. 83, 392–403 (2013).

    Article  CAS  PubMed  Google Scholar 

  98. Sallustio, F. et al. TLR2 plays a role in the activation of human resident renal stem/progenitor cells. FASEB J. 24, 514–525 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Faubel, S. et al. Caspase-1-deficient mice are protected against cisplatin-induced apoptosis and acute tubular necrosis. Kidney Int. 66, 2202–2213 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Pulskens, W. P. et al. TLR4 promotes fibrosis but attenuates tubular damage in progressive renal injury. J. Am. Soc. Nephrol. 21, 1299–1308 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pulskens, W. P. et al. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction. PLoS ONE 9, e85775 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Leemans, J. C. et al. The role of Toll-like receptor 2 in inflammation and fibrosis during progressive renal injury. PLoS ONE 4, e5704 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Campbell, M. T. et al. Toll-like receptor 4: a novel signaling pathway during renal fibrogenesis. J. Surg. Res. 168, e61–e69 (2011).

    Article  CAS  PubMed  Google Scholar 

  104. Skuginna, V. et al. Toll-Like receptor signaling and SIGIRR in renal fibrosis upon unilateral ureteral obstruction. PLoS ONE 6, e19204 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Vilaysane, A. et al. The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J. Am. Soc. Nephrol. 21, 1732–1744 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wang, W. et al. Inflammasome-independent NLRP3 augments TGF-β signaling in kidney epithelium. J. Immunol. 190, 1239–1249 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Babelova, A. et al. Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J. Biol. Chem. 284, 24035–24048 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lin, M. et al. Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy. J. Am. Soc. Nephrol. 23, 86–102 (2012).

    Article  CAS  PubMed  Google Scholar 

  109. Lin, M. et al. The TLR4 antagonist CRX-526 protects against advanced diabetic nephropathy. Kidney Int. 83, 887–900 (2013).

    Article  CAS  PubMed  Google Scholar 

  110. Kuwabara, T. et al. Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice. Diabetologia 55, 2256–2266 (2012).

    Article  CAS  PubMed  Google Scholar 

  111. Mudaliar, H. et al. The role of Toll-like receptor proteins (TLR) 2 and 4 in mediating inflammation in proximal tubules. Am. J. Physiol. Renal Physiol. 305, F143–F154 (2013).

    Article  CAS  PubMed  Google Scholar 

  112. Devaraj, S. et al. Knockout of toll-like receptor-2 attenuates both the proinflammatory state of diabetes and incipient diabetic nephropathy. Arterioscler. Thromb. Vasc. Biol. 31, 1796–804 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Kaur, H., Chien, A. & Jialal, I. Hyperglycemia induces Toll like receptor 4 expression and activity in mouse mesangial cells: relevance to diabetic nephropathy. Am. J. Physiol. Renal Physiol. 303, F1145–F1150 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Cha, J. J. et al. Renal protective effects of toll-like receptor 4 signaling blockade in type 2 diabetic mice. Endocrinology 154, 2144–2155 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Chen, K. et al. ATP-P2X4 signaling mediates NLRP3 inflammasome activation: a novel pathway of diabetic nephropathy. Int. J. Biochem. Cell Biol. 45, 932–943 (2013).

    Article  CAS  PubMed  Google Scholar 

  116. Wang, C., Pan, Y., Zhang, Q. Y., Wang, F. M. & Kong, L. D. Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS ONE 7, e38285 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Du, P. et al. NOD2 promotes renal injury by exacerbating inflammation and podocyte insulin resistance in diabetic nephropathy. Kidney Int. 84, 265–276 (2013).

    Article  CAS  PubMed  Google Scholar 

  118. Zhang, C. et al. Activation of Nod-like receptor protein 3 inflammasomes turns on podocyte injury and glomerular sclerosis in hyperhomocysteinemia. Hypertension 60, 154–162 (2012).

    Article  CAS  PubMed  Google Scholar 

  119. Hu, Q. H., Zhang, X., Pan, Y., Li, Y. C. & Kong, L. D. Allopurinol, quercetin and rutin ameliorate renal NLRP3 inflammasome activation and lipid accumulation in fructose-fed rats. Biochem. Pharmacol. 84, 113–125 (2012).

    Article  CAS  PubMed  Google Scholar 

  120. Bakker, P. J. et al. Nlrp3 is a key modulator of diet-induced nephropathy and renal cholesterol accumulation. Kidney Int. 85, 1112–1122 (2014).

    Article  CAS  PubMed  Google Scholar 

  121. Akahoshi, T., Murakami, Y. & Kitasato, H. Recent advances in crystal-induced acute inflammation. Curr. Opin. Rheumatol. 19, 146–150 (2007).

    Article  CAS  PubMed  Google Scholar 

  122. Kurts, C. A crystal-clear mechanism of chronic kidney disease. Kidney Int. 84, 859–861 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Mulay, S. R. et al. Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion. J. Clin. Invest. 123, 236–246 (2013).

    Article  CAS  PubMed  Google Scholar 

  124. Knauf, F. et al. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 84, 895–901 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Anders, H. J. & Lech, M. NOD-like and Toll-like receptors or inflammasomes contribute to kidney disease in a canonical and a non-canonical manner. Kidney Int. 84, 225–228 (2013).

    Article  CAS  PubMed  Google Scholar 

  126. Mulay, S. R., Evan, A. & Anders, H. J. Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease. Nephrol. Dial. Transplant. 29, 507–514 (2013).

    Article  CAS  PubMed  Google Scholar 

  127. Correa-Costa, M. et al. Pivotal role of Toll-like receptors 2 and 4, its adaptor molecule MyD88, and inflammasome complex in experimental tubule-interstitial nephritis. PLoS ONE 6, e29004 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Darisipudi, M. N. et al. Uromodulin triggers IL-1β-dependent innate immunity via the NLRP3 inflammasome. J. Am. Soc. Nephrol. 23, 1783–1789 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Saemann, M. D. et al. Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism. J. Clin. Invest. 115, 468–475 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Wang, S. et al. Recipient Toll-like receptors contribute to chronic graft dysfunction by both MyD88- and TRIF-dependent signaling. Dis. Model. Mech. 3, 92–103 (2010).

    Article  CAS  PubMed  Google Scholar 

  131. Lim, S. W. et al. Cyclosporine-induced renal injury induces toll-like receptor and maturation of dendritic cells. Transplantation 80, 691–699 (2005).

    Article  CAS  PubMed  Google Scholar 

  132. Braudeau, C. et al. Contrasted blood and intragraft toll-like receptor 4 mRNA profiles in operational tolerance versus chronic rejection in kidney transplant recipients. Transplantation 86, 130–136 (2008).

    Article  CAS  PubMed  Google Scholar 

  133. Christensen, S. R. et al. Toll-like receptor 9 controls anti-DNA autoantibody production in murine lupus. J. Exp. Med. 202, 321–331 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Marshak-Rothstein, A. & Rifkin, I. R. Immunologically active autoantigens: the role of toll-like receptors in the development of chronic inflammatory disease. Annu. Rev. Immunol. 25, 419–441 (2007).

    Article  CAS  PubMed  Google Scholar 

  135. Patole, P. S. et al. Expression and regulation of Toll-like receptors in lupus-like immune complex glomerulonephritis of MRL-Fas(lpr) mice. Nephrol. Dial. Transplant. 21, 3062–3073 (2006).

    Article  CAS  PubMed  Google Scholar 

  136. Wu, X. & Peng, S. L. Toll-like receptor 9 signaling protects against murine lupus. Arthritis Rheum. 54, 336–342 (2006).

    Article  CAS  PubMed  Google Scholar 

  137. Savarese, E. et al. Requirement of Toll-like receptor 7 for pristane-induced production of autoantibodies and development of murine lupus nephritis. Arthritis Rheum. 58, 1107–1115 (2008).

    Article  CAS  PubMed  Google Scholar 

  138. Lau, C. M. et al. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J. Exp. Med. 202, 1171–1177 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Leadbetter, E. A. et al. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603–607 (2002).

    Article  CAS  PubMed  Google Scholar 

  140. Migliorini, A. & Anders, H. J. A novel pathogenetic concept-antiviral immunity in lupus nephritis. Nat. Rev. Nephrol. 8, 183–189 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Anders, H. J. et al. Activation of toll-like receptor-9 induces progression of renal disease in MRL-Fas(lpr) mice. FASEB J. 18, 534–536 (2004).

    Article  CAS  PubMed  Google Scholar 

  142. Pawar, R. D. et al. Toll-like receptor-7 modulates immune complex glomerulonephritis. J. Am. Soc. Nephrol. 17, 141–149 (2006).

    Article  CAS  PubMed  Google Scholar 

  143. Christensen, S. R. et al. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25, 417–428 (2006).

    Article  CAS  PubMed  Google Scholar 

  144. Pawar, R. D. et al. Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus. J. Am. Soc. Nephrol. 18, 1721–1731 (2007).

    Article  CAS  PubMed  Google Scholar 

  145. Guiducci, C. et al. TLR recognition of self nucleic acids hampers glucocorticoid activity in lupus. Nature 465, 937–941 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Dong, L., Ito, S., Ishii, K. J. & Klinman, D. M. Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice. Arthritis Rheum. 52, 651–658 (2005).

    Article  CAS  PubMed  Google Scholar 

  147. Lech, M. et al. IRF4 deficiency abrogates lupus nephritis despite enhancing systemic cytokine production. J. Am. Soc. Nephrol. 22, 1443–1452 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Lech, M. et al. Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus. Ann. Rheum. Dis. 70, 2207–2217 (2011).

    Article  CAS  PubMed  Google Scholar 

  149. Lech, M. et al. Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens. J. Exp. Med. 205, 1879–1888 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Kumagai, Y. et al. Cutting edge: TLR-dependent viral recognition along with type I IFN positive feedback signaling masks the requirement of viral replication for IFN-α production in plasmacytoid dendritic cells. J. Immunol. 182, 3960–3964 (2009).

    Article  CAS  PubMed  Google Scholar 

  151. Allam, R. et al. Viral 5'-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses. Eur. J. Immunol. 38, 3487–3498 (2008).

    Article  CAS  PubMed  Google Scholar 

  152. Allam, R. et al. Viral RNA and DNA trigger common antiviral responses in mesangial cells. J. Am. Soc. Nephrol. 20, 1986–1996 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Suzuki, K., Imaizumi, T., Tsugawa, K., Ito, E. & Tanaka, H. Expression of retinoic acid-inducible gene-I in lupus nephritis. Nephrol. Dial. Transplant. 22, 2407–2409 (2007).

    Article  CAS  PubMed  Google Scholar 

  154. Patole, P. S. et al. Viral double-stranded RNA aggravates lupus nephritis through Toll-like receptor 3 on glomerular mesangial cells and antigen-presenting cells. J. Am. Soc. Nephrol. 16, 1326–1338 (2005).

    Article  CAS  PubMed  Google Scholar 

  155. Patole, P. S. et al. Coactivation of Toll-like receptor-3 and -7 in immune complex glomerulonephritis. J. Autoimmun. 29, 52–59 (2007).

    Article  CAS  PubMed  Google Scholar 

  156. Wornle, M. et al. Novel role of toll-like receptor 3 in hepatitis C-associated glomerulonephritis. Am. J. Pathol. 168, 370–385 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Fu, Y. et al. Innate stimuli accentuate end-organ damage by nephrotoxic antibodies via Fc receptor and TLR stimulation and IL-1/TNF-α production. J. Immunol. 176, 632–639 (2006).

    Article  CAS  PubMed  Google Scholar 

  158. Pawar, R. D. et al. Bacterial lipopeptide triggers massive albuminuria in murine lupus nephritis by activating Toll-like receptor 2 at the glomerular filtration barrier. Immunology 128, e206–e221 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Summers, S. A. et al. TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy. J. Autoimmun. 35, 291–298 (2010).

    Article  CAS  PubMed  Google Scholar 

  160. Anders, H. J. et al. Bacterial CpG-DNA aggravates immune complex glomerulonephritis: role of TLR9-mediated expression of chemokines and chemokine receptors. J. Am. Soc. Nephrol. 14, 317–326 (2003).

    Article  CAS  PubMed  Google Scholar 

  161. Brown, H. J., Sacks, S. H. & Robson, M. G. Toll-like receptor 2 agonists exacerbate accelerated nephrotoxic nephritis. J. Am. Soc. Nephrol. 17, 1931–1939 (2006).

    Article  CAS  PubMed  Google Scholar 

  162. Suzuki, H. et al. Toll-like receptor 9 affects severity of IgA nephropathy. J. Am. Soc. Nephrol. 19, 2384–2395 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Coppo, R. et al. Toll-like receptor 4 expression is increased in circulating mononuclear cells of patients with immunoglobulin A nephropathy. Clin. Exp. Immunol. 159, 73–81 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Allam, R. & Anders, H. J. The role of innate immunity in autoimmune tissue injury. Curr. Opin. Rheumatol. 20, 538–544 (2008).

    Article  CAS  PubMed  Google Scholar 

  165. Lichtnekert, J. et al. Trif is not required for immune complex glomerulonephritis: dying cells activate mesangial cells via Tlr2/Myd88 rather than Tlr3/Trif. Am. J. Physiol. Renal Physiol. 296, 867–74 (2009).

    Article  CAS  Google Scholar 

  166. Brown, H. J. et al. Toll-like receptor 4 ligation on intrinsic renal cells contributes to the induction of antibody-mediated glomerulonephritis via CXCL1 and CXCL2. J. Am. Soc. Nephrol. 18, 1732–1739 (2007).

    Article  CAS  PubMed  Google Scholar 

  167. Brown, H. J., Lock, H. R., Sacks, S. H. & Robson, M. G. TLR2 stimulation of intrinsic renal cells in the induction of immune-mediated glomerulonephritis. J. Immunol. 177, 1925–1931 (2006).

    Article  CAS  PubMed  Google Scholar 

  168. Machida, H. et al. Expression of Toll-like receptor 9 in renal podocytes in childhood-onset active and inactive lupus nephritis. Nephrol. Dial. Transplant. 25, 2530–2537 (2010).

    Article  CAS  PubMed  Google Scholar 

  169. Banas, M. C. et al. TLR4 links podocytes with the innate immune system to mediate glomerular injury. J. Am. Soc. Nephrol. 19, 704–713 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Kiberd, B. A. & Stadnyk, A. W. Established murine lupus nephritis does not respond to exogenous interleukin-1 receptor antagonist; a role for the endogenous molecule? Immunopharmacology 30, 131–137 (1995).

    Article  CAS  PubMed  Google Scholar 

  171. Reilly, M. et al. Randomized, double-blind, placebo-controlled, dose-escalating phase I, healthy subjects study of intravenous OPN-305, a humanized anti-TLR2 antibody. Clin. Pharmacol. Ther. 94, 593–600 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Hu, Y. M., Pai, M. H., Yeh, C. L., Hou, Y. C. & Yeh, S. L. Glutamine administration ameliorates sepsis-induced kidney injury by downregulating the high-mobility group box protein-1-mediated pathway in mice. Am. J. Physiol. Renal Physiol. 302, F150–F158 (2012).

    Article  CAS  PubMed  Google Scholar 

  173. Harrison, E. M. et al. Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol. 295, F397–F405 (2008).

    Article  CAS  PubMed  Google Scholar 

  174. Packard, A. E. et al. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury. J. Cereb. Blood Flow Metab. 32, 242–247 (2012).

    Article  CAS  PubMed  Google Scholar 

  175. Liu, M. et al. Protective effects of Toll-like receptor 4 inhibitor eritoran on renal ischemia-reperfusion injury. Transplant. Proc. 42, 1539–1544 (2010).

    Article  CAS  PubMed  Google Scholar 

  176. Opal, S. M. et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 309, 1154–1162 (2013).

    Article  CAS  PubMed  Google Scholar 

  177. Brumbaugh, A. R. & Mobley, H. L. T. Preventing urinary tract infection: progress toward an effective Escherichia coli vaccine. Expert Rev. Vaccines 11, 663–676 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Harberts, E. & Gaspari, A. A. TLR signaling and DNA repair: are they associated? J. Invest. Dermatol. 133, 296–302 (2013).

    Article  CAS  PubMed  Google Scholar 

  179. Rakoff-Nahoum, S. & Medzhitov, R. Role of toll-like receptors in tissue repair and tumorigenesis. Biochem. (Mosc.) 73, 555–561 (2008).

    Article  CAS  Google Scholar 

  180. Kuo, M. C. et al. Ischemia-induced exocytosis of Weibel-Palade bodies mobilizes stem cells. J. Am. Soc. Nephrol. 19, 2321–2330 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Romagnani, P. & Anders, H.-J. What can tubular progenitor cultures teach us about kidney regeneration? Kidney Int. 83, 351–353 (2013).

    Article  CAS  PubMed  Google Scholar 

  182. Kim, B. S. et al. Ischemia-reperfusion injury activates innate immunity in rat kidneys. Transplantation 79, 1370–1377 (2005).

    Article  PubMed  Google Scholar 

  183. Bergler, T. et al. Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals. Nephron Exp. Nephrol. 121, 59–70 (2012).

    Article  CAS  Google Scholar 

  184. Benigni, A. et al. Involvement of renal tubular Toll-like receptor 9 in the development of tubulointerstitial injury in systemic lupus. Arthritis Rheum. 56, 1569–78 (2007).

    Article  CAS  PubMed  Google Scholar 

  185. Papadimitraki, E. D., Tzardi, M., Bertsias, G., Sotsiou, E. & Boumpas, D. T. Glomerular expression of toll-like receptor-9 in lupus nephritis but not in normal kidneys: implications for the amplification of the inflammatory response. Lupus 18, 831–835 (2009).

    Article  CAS  PubMed  Google Scholar 

  186. Lichtnekert, J. et al. Anti-GBM glomerulonephritis involves IL-1 but is independent of NLRP3/ASC inflammasome-mediated activation of caspase-1. PLoS ONE 6, e26778 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Tsai, P.-Y. et al. Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation. Free Radic. Biol. Med. 51, 744–754 (2011).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

J.C.L. and L.K. have received support from the Netherlands Organization for Scientific Research (grant 016.126.386). J.C.L. is supported by the Dutch Kidney Foundation (grants C06.6023 and C10.2350) and H.-J.A. by the Deutsche Forschungsgemeinschaft (grants AN372/9-2 and AN327/14-1).

Author information

Authors and Affiliations

  1. Department of Pathology, Academic Medical Center, Meibergdreef 9, L2-111, Amsterdam, 1105 AZ, Netherlands

    Jaklien C. Leemans, Lotte Kors & Sandrine Florquin

  2. Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstraße 1, München, 80336, Germany

    Hans-Joachim Anders

Authors
  1. Jaklien C. Leemans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lotte Kors
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans-Joachim Anders
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sandrine Florquin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched the data for the article and wrote, reviewed and edited the manuscript before submission. H.-J.A. and S.F. contributed equally to this manuscript.

Corresponding author

Correspondence to Jaklien C. Leemans.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Leemans, J., Kors, L., Anders, HJ. et al. Pattern recognition receptors and the inflammasome in kidney disease. Nat Rev Nephrol 10, 398–414 (2014). https://doi.org/10.1038/nrneph.2014.91

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneph.2014.91

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing