Figure 10.

Summary of the TLR3, TLR7, and TLR8 pathways regulating neuronal morphology. TLR3, TLR7, and TLR8 all use MYD88 to control the downstream pathways regulating neuronal morphology, although TRIF is critical for TLR3 to regulate cytokine expression in neurons (Chen et al., 2017). The colored ellipses indicate the major biological processes of target genes downstream of TLR3 (blue), TLR7 (green), and TLR8 (red). Some ellipses overlap because some target genes are shared between different pathways, particularly for inflammatory and innate immune responses downstream of TLR3 and TLR7. For TLR3 and TLR8, only four genes (namely Prex2, Jag1, Cdk6, and Ccnd1) overlap among these top GO processes. The specific agonists and ligands of TLR3, TLR7, and TLR8 are also labeled. The effects of TLR3, TLR7, and TLR8 on neuronal morphology are indicated at bottom. For TLR8, MYD88, TAK1, and P38, MAPKs are required for dendritic pruning. MYD88 and DISC1 are required for TLR3-mediated neuronal morphogenesis (Chen et al., 2017). The biological function of cytokines or innate immune responses induced by the TLR3–TRIF pathway in neurons is unclear. TLR7 uses a traditional pathway involving in MYD88, c-FOS, and IL-6 to negatively regulate dendritic and axonal outgrowth in neurons (Liu et al., 2013).