TLR2 and NODs1 and 2 cooperate in inflammatory responses associated with renal ischemia reperfusion injury.

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.

• Authors: Sashi G Kasimsetty, Alana Hawkes, Kayvan Barekatain, Elizabeth Soo, Alexander K Welch, Dianne B McKay
• Journal: Transplant immunology (Transpl Immunol) Vol. 58 Pg. 101260 (02 2020) ISSN: 1878-5492 [Electronic] Netherlands
• PMID: 31760144 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• Nod1 Signaling Adaptor Protein
• Nod1 protein, mouse
• Nod2 Signaling Adaptor Protein
• Nod2 protein, mouse
• TLR2 protein, human
• Toll-Like Receptor 2

Topics

• Animals
• Humans
• Immunity, Innate
• Inflammation (metabolism)
• Kidney (immunology, surgery)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Cells (immunology)
• Nod1 Signaling Adaptor Protein (genetics, metabolism)
• Nod2 Signaling Adaptor Protein (genetics, metabolism)
• Reperfusion Injury (metabolism)
• Signal Transduction
• Toll-Like Receptor 2 (genetics, metabolism)