CX3CR1 modulates migration of resident microglia towards brain injury

Microglia are innate immune cells of the central nervous system (CNS). They extend their processes towards and migrate towards injuries in vivo. However, whether the fractalkine receptor (CX3CR1) influences microglial migration remains unknown. Label-free proteomic profiling predicted changes in RHO-signaling activity that hint at dysregulated cytoskeleton signaling in Cx3cr1-deficient murine cortex tissue. To further investigate microglial migration, we carried out 4-hour interval two-photon in vivo imaging for 72 hours after a laser lesion in the cortex. Cx3cr1-deficient microglia showed enhanced migration towards the lesion. Additionally, length and velocity of microglial fine processes extending towards the lesion were increased in Cx3cr1-deficient microglia. Migration remained unchanged in Ccr2-deficient mice, indicating that monocyte-derived macrophages/microglia did not contribute to microglia accumulation around the lesion. These results demonstrate microglia migration towards CNS injury and suggest CX3CR1 as a modulator of this. Manipulating microglia migration via CX3CR1 therefore is a potential target for treatment of CNS-injury.