title: TLR2 controls random motility, while TLR7 regulates chemotaxis of microglial cells via distinct pathways.
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.
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ifuku
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Buonfiglioli
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jordan
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin, Berlin, Germany; Department of Neurology, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Seija
authors.initials: S
authors.lastname: Lehnardt
authors.affiliation: Cellular Neuroscience, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. Electronic address: kettenmann@mdc-berlin.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
mesh_terms: D000818:Animals; D002465:Cell Movement; D002633:Chemotaxis; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D058925:Receptors, Purinergic P2Y12; C493486:Tlr2 protein, mouse; C477038:Tlr7 protein, mouse; D051195:Toll-Like Receptor 2; D051199:Toll-Like Receptor 7; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Chemotaxis; Migration; PI3K; Rac; Toll-like receptor