Local migration and proliferation of resident microglia after a laser lesion is dependent on CX3CR1
1 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
2 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
3 Institute of Molecular Medicine and Experimental Immunology, University Bonn, Germany
Microglia are the innate immune cells of the brain. Microglia are highly motile cells that screen the surrounding brain parenchyma with their processes on a minute time-scale. It is well-established that microglia extend their processes towards lesions in the central nervous system (CNS) and accumulate around these lesions. To investigate the origin of the accumulating microglia, we carried out repetitive two-photon in vivo imaging of microglia for 72 hours after induction of a laser lesion in the CNS. Interestingly, we observed that the accumulation of microglia around the lesion resulted predominantly from migration of previously sessile microglia. In the 72-hour period after the laser lesion, microglia migrated with a high directionality. A key factor in microglial migration is the fractalkine receptor (CX3CR1). In CX3CR1-knockout mice, we found that migration towards the lesion was changed in CX3CR1 deficient mice. The distance travelled towards the lesion and migration velocity were increased in the CX3CR1-knockout animals. Not only cell body migration, but also length and velocity of the microglial processes extended towards the lesion were increased in the CX3CR1 knockout. By an additional knockout of the CCR2 receptor, we ruled out a contribution of inflammatory monocytes demonstrating that the local accumulation around the lesion is caused by migration and proliferation of resident microglia rather than monocyte precursors recruited from the blood. These results indicate a role for CX3CR1 in influencing microglia migration, which may become important for manipulating microglia migration as a treatment strategy for a variety of neuro-inflammatory conditions.