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Published on: July 26, 2017
[Toll-like receptors (TLR) in the pathogenesis of kidney diseases]
Krzysztof Kazimierczak1, Wacław Kopeć, Marian Klinger
1Akademia Medyczna we Wrocławiu, Katedra i Klinika Nefrologii i Medycyny Transplantacyjnej. klinef@neph.am.wroc.pl
Abstract:
In the present work general characteristics and occurrence of TLR receptors have been presented. The participation of TLR receptors in kidney pathology in experimental models in the course of urinary system infection, acute renal failure and interstitial fibrosis has been discussed. In addition, the importance of TLRs in various forms of glomerular nephritis and in haemodialytic patients as well as in postrenal-transplant patients has been shown. It is believed that in lipopolysaccharide-induced renal failure in the course of infections caused by Gram negative bacteria TLR4 plays a fundamental role. In the event of damage of renal tubular epithelial cells by mechanical, toxic, or ischemic factors activation of TLRs induces inflammatory processes leading to acute renal failure. In the course of progressive fibrosis of renal interstitial tissue TLR 2 and 4 receptors are stimulated, which results in the fact that immunological and structural cells of renal tissue release chemokines and cytokines, which causes increased inflow of leucocytes and intensification of interstitial nephritis and progressive fibrosis. The study on experimental models on mice MLR (mixed lymphocyte reaction) with genetically conditioned lupus-like disease showed that, CpG-DNA stimulation as a TLR 9 specific agonist intensifies inflammatory symptoms in mice. Similarly in apoferritin induced glomerulopathy (model of immune complex disease) CpG-DNA nucleotide increased glomerulopathy symptoms. It has been proved that activation of mechanisms of inherent immunity through TLR4 receptors affects the frequency and intensity of acute rejections in human organ transplantations. Incidence of acute kidney and lung [transplant rejections was significantly lower in recipients with mutated variants of Toll-like receptor 4 (TLR-4 Asp 299Gly and TLR-4-Tyr399-IIe).
Insights
Toll-like receptors (TLRs) play a crucial role in kidney diseases, including infections and fibrosis. Specific TLRs, like TLR4, are implicated in acute renal failure and transplant rejection, with certain mutations potentially reducing rejection incidence.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Context:
- Toll-like receptors (TLRs) are key components of the innate immune system involved in pathogen recognition and immune response.
- Kidney diseases, including urinary tract infections, acute renal failure, interstitial fibrosis, and glomerulonephritis, involve complex inflammatory pathways.
- TLRs have been identified as critical mediators in various kidney pathologies and in the context of organ transplantation.
Purpose:
- To present the general characteristics and occurrence of TLR receptors.
- To discuss the participation of TLR receptors in experimental models of kidney pathology, including urinary system infection, acute renal failure, and interstitial fibrosis.
- To highlight the role of TLRs in different forms of glomerulonephritis, in hemodialysis patients, and post-renal transplant patients.
Summary:
- TLR4 is fundamental in lipopolysaccharide-induced renal failure from Gram-negative bacterial infections.
- Activation of TLRs by mechanical, toxic, or ischemic damage to renal tubular epithelial cells initiates inflammatory processes leading to acute renal failure.
- TLR 2 and 4 stimulation in progressive renal interstitial fibrosis leads to chemokine and cytokine release, increasing leukocyte influx and exacerbating interstitial nephritis.
- CpG-DNA, a TLR 9 agonist, intensifies inflammatory symptoms in experimental models of lupus-like disease and immune complex glomerulopathy.
- Activation of innate immunity via TLR4 influences the frequency and intensity of acute organ transplant rejections.
Impact:
- Understanding TLR involvement in kidney pathology can lead to targeted therapeutic strategies for renal diseases.
- Genetic variations in TLR4 may influence susceptibility and outcomes in organ transplantation, suggesting potential for personalized medicine approaches.
- This research underscores the significance of TLRs as therapeutic targets for managing inflammatory kidney diseases and improving transplant success rates.
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