title: Differential role of CCR2 in the dynamics of microglia and perivascular macrophages during prion disease.
abstract: The expansion of the microglial population is one of the hallmarks of numerous brain disorders. The addition of circulating progenitors to the pool of brain macrophages can contribute to the progression of brain disease and needs to be precisely defined to better understand the evolution of the glial and inflammatory reactions in the brain. We have analyzed the degree of infiltration/recruitment of circulating monocytes to the microglial pool, in a prion disease model of chronic neurodegeneration. Our results indicate a minimal/absent level of CCR2-dependent recruitment of circulating monocytes, local proliferation of microglia is the main driving force maintaining the amplification of the population. A deficiency in CCR2, and thus the absence of recruitment of circulating monocytes, does not impact microglial dynamics, the inflammatory profile or the temporal behavioral course of prion disease. However, the lack of CCR2 has unexpected effects including the failure to recruit perivascular macrophages in diseased but not healthy CNS and a small reduction in microglia proliferation. These data define the composition of the CNS-resident macrophage populations in prion disease and will help to understand the dynamics of the CNS innate immune response during chronic neurodegeneration.
authors.affiliation: Centre for Biological Sciences, University of Southampton, United Kingdom.
authors.forename: Diego
authors.initials: D
authors.lastname: Gómez-Nicola
authors.forename: Sjoerd T T
authors.initials: ST
authors.lastname: Schetters
authors.forename: V Hugh
authors.initials: VH
authors.lastname: Perry
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000276:immunology*; D049109:Cell Proliferation; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008264:Macrophages / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D019636:Neurodegenerative Diseases / Q000276:immunology; D017096:Prion Diseases / Q000276:immunology*; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2
keywords: CCR2−/−; ME7 model; circulating monocytes; microglial proliferation; neurodegeneration