In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed

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. GLIA 2014;62:1724–1735