Related Experiment Video
Updated: Jan 3, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
TLR2 and NODs1 and 2 cooperate in inflammatory responses associated with renal ischemia reperfusion injury
Sashi G Kasimsetty1, Alana Hawkes2, Kayvan Barekatain3
1Department of Immunology and Microbial Sciences, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, United States of America.
Abstract:
Pattern recognition receptors (PRRs) are potent triggers of tissue injury following renal ischemia/reperfusion injury (IRI). Specific PRRs, such as the toll-like receptor 2 (TLR2) and the nucleotide-binding oligomerization domain-like receptors (NLRs) NOD1 and NOD2 are promising targets to abrogate inflammatory injury associated with renal IRI. Several recent reports have shown there is crosstalk between TLRs and NODs, which might boost inflammatory responses to tissue injury. This study examined the relative roles of TLR2 and NODs 1 and 2 in activation of myeloid cells that contribute to inflammation after renal IRI. We found that TLR2 and NOD1 and 2 signaling induces neutrophil, macrophage and dendritic cell migration in vitro, however their blockade only decreases neutrophil infiltration into ischemic kidneys. The results of this study suggest that future therapies targeted to innate immune blockade should consider that either TLR2 or NOD1/2 blockade could decrease neutrophil inflammation following an ischemic insult to the kidney, however blockade of these PRRs would not likely impact infiltration of dendritic cells or macrophages. Developing rational approaches that target innate immunity in IRI-induced acute kidney injury requires an understanding of the relative role of PRRs in directing inflammation in the kidney.
Insights
Pattern recognition receptors (PRRs) like TLR2 and NODs trigger kidney injury. Blocking TLR2 or NODs reduces neutrophil infiltration in renal ischemia/reperfusion injury (IRI), but not other immune cells.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Pattern recognition receptors (PRRs) activate inflammatory responses.
- Renal ischemia/reperfusion injury (IRI) involves PRRs like toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-like receptors (NLRs).
- Crosstalk between TLRs and NLRs may exacerbate inflammation in tissue injury.
Purpose of the Study:
- To investigate the specific roles of TLR2, NOD1, and NOD2 in myeloid cell activation during renal IRI.
- To determine the impact of blocking these PRRs on immune cell infiltration in the kidneys.
Main Methods:
- In vitro analysis of myeloid cell migration induced by TLR2, NOD1, and NOD2 signaling.
- In vivo assessment of immune cell infiltration in kidneys following renal IRI with PRR blockade.
Main Results:
- TLR2, NOD1, and NOD2 signaling promoted neutrophil, macrophage, and dendritic cell migration in vitro.
- Blockade of TLR2 or NOD1/2 significantly reduced neutrophil infiltration into ischemic kidneys.
- Dendritic cell and macrophage infiltration remained unaffected by PRR blockade.
Conclusions:
- TLR2 and NOD1/2 signaling play distinct roles in mediating inflammation after renal IRI.
- Targeting TLR2 or NOD1/2 may be beneficial for reducing neutrophil-driven inflammation in acute kidney injury.
- Therapeutic strategies should consider the specific roles of PRRs in directing different immune cell types during renal IRI.
Related Concept Videos
01:29Acute Kidney Injury II: Pathophysiology
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...