Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons. Agonist stimulation of TLR8 in cultured cortical neurons causes inhibition of neurite outgrowth and induces apoptosis in a dissociable manner. Our evidence indicates that such TLR8-mediated neuronal responses do not involve the canonical TLR–NF-κB signaling pathway. These findings reveal novel functions for TLR8 in the mammalian nervous system that are distinct from the classical role of TLRs in immunity.
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23 October 2006
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October 23 2006
Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis
Yinghua Ma,
Yinghua Ma
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
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Jianxue Li,
Jianxue Li
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
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Isaac Chiu,
Isaac Chiu
4Center for Blood Research, Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115
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Yawen Wang,
Yawen Wang
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
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Jacob A. Sloane,
Jacob A. Sloane
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
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Jining Lü,
Jining Lü
5Pulmonary Center, Boston University School of Medicine, Boston, MA 02118
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Bela Kosaras,
Bela Kosaras
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
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Richard L. Sidman,
Richard L. Sidman
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
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Joseph J. Volpe,
Joseph J. Volpe
2Program in Neuroscience
6Department of Neurology, Children's Hospital, Boston, MA 02115
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Timothy Vartanian
Timothy Vartanian
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
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Yinghua Ma
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
Jianxue Li
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
Isaac Chiu
4Center for Blood Research, Graduate Program in Immunology, Harvard Medical School, Boston, MA 02115
Yawen Wang
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
Jacob A. Sloane
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
Jining Lü
5Pulmonary Center, Boston University School of Medicine, Boston, MA 02118
Bela Kosaras
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
Richard L. Sidman
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
Joseph J. Volpe
2Program in Neuroscience
6Department of Neurology, Children's Hospital, Boston, MA 02115
Timothy Vartanian
1Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115
2Program in Neuroscience
3Center for Neurodegeneration and Repair,
Correspondence to Timothy Vartanian: [email protected]
Abbreviations used in this paper: CNS, central nervous system; DIG, digoxin; DIV, days in vitro; E, embryonic day; IRAK, interleukin-1 receptor–associated kinase; LPS, lipopolysaccharide; NF-κB, nuclear factor-κB; P, postnatal day; PAMPs, pathogen-associated molecular patterns; TLRs, Toll-like receptors.
Received:
June 05 2006
Accepted:
September 11 2006
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2006
J Cell Biol (2006) 175 (2): 209–215.
Article history
Received:
June 05 2006
Accepted:
September 11 2006
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Citation
Yinghua Ma, Jianxue Li, Isaac Chiu, Yawen Wang, Jacob A. Sloane, Jining Lü, Bela Kosaras, Richard L. Sidman, Joseph J. Volpe, Timothy Vartanian; Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis . J Cell Biol 23 October 2006; 175 (2): 209–215. doi: https://doi.org/10.1083/jcb.200606016
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