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Identification of CNS Injury-Related microRNAs as Novel Toll-Like Receptor 7/8 Signaling Activators by Small RNA Sequencing

Wallach, Thomas, Wetzel, Max, Dembny, Paul, Staszewski, Ori, Krüger, Christina, Buonfiglioli, Alice, Prinz, Marco, Lehnardt, Seija·2020·Cells
DOI 10.3390/cells9010186PMC PMC7017345
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Abstract

Toll-like receptors (TLRs) belong to pattern recognition receptors, which respond to danger signals such as pathogen-associated molecular patterns or damage-associated molecular patterns. Upon TLR activation in microglia, the major immune cells in the brain, distinct signaling cascades trigger the production of inflammatory molecules, being a critical feature in neuroinflammation and neurodegenerative processes. Recently, individual microRNAs (miRNAs) were shown to act as endogenous TLR ligands. Here, we conducted systematic screening for miRNAs as potential TLR7/8 ligands by small RNA sequencing of apoptotic neurons and their corresponding supernatants. Several miRNA species were identified in both supernatants and injured neurons, and 83.3% of the media-enriched miRNAs activated murine and/or human TLR7/8 expressed in HEK293-derived TLR reporter cells. Among the detected extracellular miRNAs, distinct miRNAs such as miR-340-3p and miR-132-5p induced cytokine and chemokine release from microglia and triggered neurotoxicity in vitro. Taken together, our systematic study establishes miRNAs released from injured neurons as new TLR7/8 activators, which contribute to inflammatory and neurodegenerative responses in the central nervous system (CNS).

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  1. Kielian, T. (2009). Overview of Toll-Like Receptors in the CNS, in Toll-like Receptors: Roles in Infection and Neuropathology, Springer. · DOI
  2. Kawai, 2010, The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors, Nat. Immunol., 11, 373, 10.1038/ni.1863 · DOI · Paper page
  3. Forsbach, 2008, Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses, J. Immunol., 180, 3729, 10.4049/jimmunol.180.6.3729 · DOI · Paper page
  4. Heil, 2004, Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8, Science, 303, 1526, 10.1126/science.1093620 · DOI · Paper page
  5. Lund, 2004, Recognition of single-stranded RNA viruses by Toll-like receptor 7, Proc. Natl. Acad. Sci. USA, 101, 5598, 10.1073/pnas.0400937101 · DOI
  6. Diebold, 2004, Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA, Science, 303, 1529, 10.1126/science.1093616 · DOI · Paper page
  7. Lehmann, 2012, An unconventional role for miRNA: Let-7 activates Toll-like receptor 7 and causes neurodegeneration, Nat. Neurosci., 15, 827, 10.1038/nn.3113 · DOI · Paper page
  8. Gaudet, 2017, MicroRNAs: Roles in Regulating Neuroinflammation, Neurosci., 24, 221
  9. Derkow, K., Rössling, R., Schipke, C., Krüger, C., Bauer, J., Fähling, M., Stroux, A., Schott, E., Ruprecht, K., and Peters, O. (2018). Distinct expression of the neurotoxic microRNA family let-7 in the cerebrospinal fluid of patients with Alzheimer’s disease. PLoS ONE, 13. · DOI
  10. Glynn, 2013, Isolation of Secreted microRNAs (miRNAs) from Cell-conditioned Media, MicroRNA, 2, 14, 10.2174/2211536611302010003 · DOI
  11. Vlachos, 2015, DIANA-miRPath v3.0: Deciphering microRNA function with experimental support, Nucleic Acids Res., 43, W460, 10.1093/nar/gkv403 · DOI
  12. Koh, 1995, Staurosporine-Induced Neuronal Apoptosis, Exp. Neurol., 135, 153, 10.1006/exnr.1995.1074 · DOI
  13. Krohn, 1998, Staurosporine-Induced Apoptosis of Cultured Rat Hippocampal Neurons Involves Caspase-1-Like Proteases as Upstream Initiators and Increased Production of Superoxide as a Main Downstream Effector, J. Neurosci., 18, 8186, 10.1523/JNEUROSCI.18-20-08186.1998 · DOI
  14. Ferrer, 2000, Staurosporine- and H-7-induced cell death in SH-SY5Y neuroblastoma cells is associated with caspase-2 and caspase-3 activation, but not with activation of the FAS/FAS-L-caspase-8 signaling pathway, Mol. Brain Res., 85, 61, 10.1016/S0169-328X(00)00235-7 · DOI
  15. Deshmukh, 2000, Staurosporine-induced neuronal death: Multiple mechanisms and methodological implications, Cell Death Differ., 7, 250, 10.1038/sj.cdd.4400641 · DOI
  16. Cao, 2008, Toll-like receptor–mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI (3) K-mTOR-p70S6K pathway, Nat. Immunol., 9, 1157, 10.1038/ni.1645 · DOI
  17. Akira, 2004, Toll-like receptor signalling, Nat. Rev. Immunol., 4, 499, 10.1038/nri1391 · DOI · Paper page
  18. Jurk, 2002, Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848, Nat. Immunol., 3, 499, 10.1038/ni0602-499 · DOI · Paper page
  19. Heil, 2003, The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily, Eur. J. Immunol., 33, 2987, 10.1002/eji.200324238 · DOI
  20. Lu, 2012, VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC, Clin. Cancer Res., 18, 499, 10.1158/1078-0432.CCR-11-1625 · DOI
  21. Liu, 2010, A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition, Mol. Immunol., 47, 1083, 10.1016/j.molimm.2009.11.003 · DOI
  22. Olson, 2004, Microglia Initiate Central Nervous System Innate and Adaptive Immune Responses through Multiple TLRs, J. Immunol., 173, 3916, 10.4049/jimmunol.173.6.3916 · DOI · Paper page
  23. Zarember, 2002, Tissue Expression of Human Toll-Like Receptors and Differential Regulation of Toll-Like Receptor mRNAs in Leukocytes in Response to Microbes, Their Products, and Cytokines, J. Immunol., 168, 554, 10.4049/jimmunol.168.2.554 · DOI
  24. Wang, 2006, The functional effects of physical interactions among Toll-like receptors 7, 8, and 9, J. Biol. Chem., 281, 37427, 10.1074/jbc.M605311200 · DOI
  25. Lehmann, 2012, Extracellularly Delivered Single-Stranded Viral RNA Causes Neurodegeneration Dependent on TLR7, J. Immunol., 189, 1448, 10.4049/jimmunol.1201078 · DOI · Paper page
  26. Lehnardt, 2003, Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway, Proc. Natl. Acad. Sci. USA, 100, 8514, 10.1073/pnas.1432609100 · DOI · Paper page
  27. Fabbri, 2012, MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response, Proc. Natl. Acad. Sci. USA, 109, E2110, 10.1073/pnas.1209414109 · DOI · Paper page
  28. Feng, 2017, Extracellular MicroRNAs Induce Potent Innate Immune Responses via TLR7/MyD88-Dependent Mechanisms, J. Immunol., 199, 2106, 10.4049/jimmunol.1700730 · DOI
  29. Pigati, L., Yaddanapudi, S.C.S., Iyengar, R., Kim, D.-J., Hearn, S.A., Danforth, D., Hastings, M.L., and Duelli , D.M. (2010). Selective Release of MicroRNA Species from Normal and Malignant Mammary Epithelial Cells. PLoS ONE, 5. · DOI
  30. Lukiw, 2007, Micro-RNA speciation in fetal, adult and Alzheimer’s disease hippocampus, NeuroReport, 18, 297, 10.1097/WNR.0b013e3280148e8b · DOI · Paper page
  31. Wang, 2017, Profiling microRNA from Brain by Microarray in a Transgenic Mouse Model of Alzheimer’s Disease, BioMed Res. Int., 2017, 8030369
  32. Qiu, 2014, Deciphering the Function and Regulation of microRNAs in Alzheimer’s Disease and Parkinson’s Disease, ACS Chem. Neurosci., 5, 884, 10.1021/cn500149w · DOI
  33. Harischandra, 2018, Environmental neurotoxicant manganese regulates exosome-mediated extracellular miRNAs in cell culture model of Parkinson’s disease: Relevance to α-synuclein misfolding in metal neurotoxicity, NeuroToxicology, 64, 267, 10.1016/j.neuro.2017.04.007 · DOI
  34. Qian, 2017, Advances in Roles of miR-132 in the Nervous System, Front. Pharmacol., 8, 770, 10.3389/fphar.2017.00770 · DOI · Paper page
  35. Miyazaki, Y., Li, R., Rezk, A., Misirliyan, H., Moore, C., Farooqi, N., Solis, M., Goiry, L.G., Junior, O.D.F., and Dang, V.D. (2014). A Novel MicroRNA-132-Surtuin-1 Axis Underlies Aberrant B-cell Cytokine Regulation in Patients with Relapsing-Remitting Multiple Sclerosis. PLoS ONE, 9. · DOI
  36. Huang, 2015, miR-340 suppresses glioblastoma multiforme, Oncotarget, 6, 9257, 10.18632/oncotarget.3288 · DOI
  37. Fernandez, 2015, miR-340 inhibits tumor cell proliferation and induces apoptosis by targeting multiple negative regulators of p27 in non-small cell lung cancer, Oncogene, 34, 3240, 10.1038/onc.2014.267 · DOI
  38. Li, 2015, miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2, Biochem. Biophys. Res. Commun., 460, 670, 10.1016/j.bbrc.2015.03.088 · DOI
  39. Shi, 2008, hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells, Brain Res., 1236, 185, 10.1016/j.brainres.2008.07.085 · DOI
  40. Moon, 2013, Inhibition of microRNA-181 Reduces Forebrain Ischemia-Induced Neuronal Loss, J. Cereb. Blood Flow Metab., 33, 1976, 10.1038/jcbfm.2013.157 · DOI

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Metadata

Authors
Wallach, T., Wetzel, M., Dembny, P., Staszewski, O., Krüger, C., Buonfiglioli, A., Prinz, M., & Lehnardt, S.
Affiliations
  • Institute of Cell Biology and Neurobiology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany
  • Institute of Neuropathology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2020-01-11
Volume
9
Issue
1
Pages
186
ISSN
2073-4409
DOI
10.3390/cells9010186
PMC
PMC7017345
Cited by
26
References
4
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Deutsche Forschungsgemeinschaft (SFB TRR167 B03)

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