title: In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed.
abstract: Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) characterized by loss of myelin accompanied by infiltration of T-lymphocytes and monocytes. Although it has been shown that these infiltrates are important for the progression of MS, the role of microglia, the resident macrophages of the CNS, remains ambiguous. Therefore, we have compared the phenotypes of microglia and macrophages in a mouse model for MS, experimental autoimmune encephalomyelitis (EAE). In order to properly discriminate between these two cell types, microglia were defined as CD11b(pos) CD45(int) Ly-6C(neg) , and infiltrated macrophages as CD11b(pos) CD45(high) Ly-6C(pos) . During clinical EAE, microglia displayed a weakly immune-activated phenotype, based on the expression of MHCII, co-stimulatory molecules (CD80, CD86, and CD40) and proinflammatory genes [interleukin-1β (IL-1β) and tumour necrosis factor- α (TNF-α)]. In contrast, CD11b(pos) CD45(high) Ly-6C(pos) infiltrated macrophages were strongly activated and could be divided into two populations Ly-6C(int) and Ly-6C(high) , respectively. Ly-6C(high) macrophages contained less myelin than Ly-6C(int) macrophages and expression levels of the proinflammatory cytokines IL-1β and TNF-α were higher in Ly-6C(int) macrophages. Together, our data show that during clinical EAE, microglia are only weakly activated whereas infiltrated macrophages are highly immune reactive.
authors: Department of Neuroscience, Section Medical Physiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: I D
authors: ID
authors: Vainchtein
authors: J
authors: J
authors: Vinet
authors: N
authors: N
authors: Brouwer
authors: S
authors: S
authors: Brendecke
authors: G
authors: G
authors: Biagini
authors: K
authors: K
authors: Biber
authors: H W G M
authors: HW
authors: Boddeke
authors: B J L
authors: BJ
authors: Eggen
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D053178:Caspase 6 / Q000378:metabolism; D002678:Chimera; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D009103:Multiple Sclerosis; D013116:Spinal Cord / Q000276:immunology
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D016207:Cytokines; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; C494192:Ly-6C antigen, mouse; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; C505516:Casp6 protein, mouse; D053178:Caspase 6
keywords: EAE; Ly-6C; macrophage; microglia; multiple sclerosis