Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

作者：Yinghua Ma, Jianxue Li, Isaac M. Chiu, Yawen Wang, Jacob A. Sloane, Jining Lü, Béla Kosaras, Richard L. Sidman, Joseph J. Volpe, Timothy Vartanian · 发表于：The Journal of Cell Biology · 年份：2006 · DOI：10.1083/jcb.200606016 · 被引用次数：275 · 研究领域：Immune Response and Inflammation、Invertebrate Immune Response Mechanisms、Aquaculture disease management and microbiota

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.