TLR2 controls random motility, while TLR7 regulates chemotaxis of microglial cells via distinct pathways

Brain Behav Immun. 2016 Nov:58:338-347. doi: 10.1016/j.bbi.2016.08.003. Epub 2016 Aug 21.

Abstract

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.

Keywords: Akt; Chemotaxis; Migration; PI3K; Rac; Toll-like receptor.

MeSH terms

  • Animals
  • Cell Movement*
  • Chemotaxis*
  • Female
  • Male
  • Membrane Glycoproteins / metabolism*
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Purinergic P2Y12 / metabolism
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 7 / metabolism*

Substances

  • Membrane Glycoproteins
  • Receptors, Purinergic P2Y12
  • Tlr2 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 7
  • Proto-Oncogene Proteins c-akt