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In Acute Experimental Autoimmune Encephalomyelitis, Infiltrating Macrophages Are Immune Activated, Whereas Microglia Remain Immune Suppressed

Vainchtein, I. D., Vinet, J., Brouwer, N., Brendecke, S., Biagini, G., Biber, K., Boddeke, H. W. G. M. & Eggen, B. J. L., Oct-2014, In : Glia. 62, 10, p. 1724-1735 12 p.

Research output: Contribution to journalArticleAcademicpeer-review

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-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha)]. In contrast, CD11b(pos) CD45(high) Ly6C(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-1 beta and TNF-alpha 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.

Original languageEnglish
Pages (from-to)1724-1735
Number of pages12
JournalGlia
Volume62
Issue number10
Publication statusPublished - Oct-2014

    Keywords

  • microglia, macrophage, Ly-6C, EAE, multiple sclerosis, EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS, CENTRAL-NERVOUS-SYSTEM, MULTIPLE-SCLEROSIS, WHITE-MATTER, CNS, INFLAMMATION, MONOCYTES, BRAIN, PATHOGENESIS, RECEPTOR

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