Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin, Berlin, Germany.
Brain Behav Immun. 2016 Nov;58:338-347. doi: 10.1016/j.bbi.2016.08.003. Epub 2016 Aug 21.
Microglial cells are the pathologic sensor of the brain, and any pathologic event triggers microglial activation, which involves migration of these cells to a lesion site. Employing different migration assays, we show that ligands for toll-like receptor (TLR) 2 stimulate random motility, while TLR7 ligands are chemoattractants. The subtype specificity of the TLR ligands was verified by using different TLR-deficient (TLRKO) mouse lines. PI3K and Rac inhibition impairs both TLR2- and TLR7-stimulated microglial migration. In contrast, Akt phosphorylation is only required for the TLR2-, but not for the TLR7-stimulated pathway. Interestingly, P2Y12 receptor signaling is involved in the TLR2 activation-induced microglial migration but not TLR7. Furthermore, TLR7 mRNA expression is down-regulated by TLR2 and TLR7 activation. We conclude that TLRs control the migratory behavior of microglia in a distinct manner.
小胶质细胞是大脑的病理传感器，任何病理事件都会触发小胶质细胞的激活，这涉及到这些细胞向病变部位的迁移。通过使用不同的迁移测定法，我们表明 Toll 样受体 (TLR) 2 的配体刺激随机运动，而 TLR7 配体则是趋化剂。通过使用不同的 TLR 缺陷 (TLRKO) 小鼠系，验证了 TLR 配体的亚型特异性。PI3K 和 Rac 抑制均损害 TLR2 和 TLR7 刺激的小胶质细胞迁移。相比之下，Akt 磷酸化仅需要 TLR2 途径，而不需要 TLR7 途径。有趣的是，P2Y12 受体信号参与 TLR2 激活诱导的小胶质细胞迁移，但不参与 TLR7。此外，TLR7 mRNA 表达受 TLR2 和 TLR7 激活的下调。我们得出结论，TLR 以不同的方式控制小胶质细胞的迁移行为。
