Ma Yinghua, Li Jianxue, Chiu Isaac, Wang Yawen, Sloane Jacob A, Lü Jining, Kosaras Bela, Sidman Richard L, Volpe Joseph J, Vartanian Timothy
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
J Cell Biol. 2006 Oct 23;175(2):209-15. doi: 10.1083/jcb.200606016.
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-kappaB 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.
黑腹果蝇中的Toll受体在形态发生和宿主防御中发挥作用。Toll的哺乳动物同源物，即Toll样受体（TLR），因其在控制先天性和适应性免疫反应中的重要功能而受到广泛研究。我们报告称，TLR8在小鼠大脑发育过程中动态表达，并定位于神经元和轴突。在培养的皮质神经元中，TLR8激动剂刺激会导致神经突生长受到抑制，并以可分离的方式诱导细胞凋亡。我们的证据表明，这种TLR8介导的神经元反应不涉及经典的TLR-NF-κB信号通路。这些发现揭示了TLR8在哺乳动物神经系统中的新功能，这些功能不同于TLR在免疫中的经典作用。
