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Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion

Cellular and Molecular Research Group, Department of Anatomy, Faculty of Medicine, Masaryk University, Kamenice 3, CZ-62500 Brno, Czech Republic
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Author to whom correspondence should be addressed.
Academic Editors: Giulia Ronchi and Ilaria Tonazzini
Int. J. Mol. Sci. 2021, 22(14), 7446; https://doi.org/10.3390/ijms22147446
Received: 29 May 2021 / Revised: 7 July 2021 / Accepted: 8 July 2021 / Published: 12 July 2021
One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)—the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury. View Full-Text
Keywords: sciatic nerve; compression; transection; mitochondrial DNA; the endoplasmic reticulum; early endosomes; axon regeneration sciatic nerve; compression; transection; mitochondrial DNA; the endoplasmic reticulum; early endosomes; axon regeneration
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MDPI and ACS Style

Dubový, P.; Hradilová-Svíženská, I.; Brázda, V.; Joukal, M. Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion. Int. J. Mol. Sci. 2021, 22, 7446. https://doi.org/10.3390/ijms22147446

AMA Style

Dubový P, Hradilová-Svíženská I, Brázda V, Joukal M. Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion. International Journal of Molecular Sciences. 2021; 22(14):7446. https://doi.org/10.3390/ijms22147446

Chicago/Turabian Style

Dubový, Petr, Ivana Hradilová-Svíženská, Václav Brázda, and Marek Joukal. 2021. "Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion" International Journal of Molecular Sciences 22, no. 14: 7446. https://doi.org/10.3390/ijms22147446

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