Macrophage subsets and microglia in multiple sclerosis

Abstract

Along with microglia and monocyte-derived macrophages, macrophages in the perivascular space, choroid plexus, and meninges are the principal effector cells in neuroinflammatory and neurodegenerative disorders. These phagocytes are highly heterogeneous cells displaying spatial- and temporal-dependent identities in the healthy, injured, and inflamed CNS. In the last decade, researchers have debated on whether phagocytes subtypes and phenotypes are pathogenic or protective in CNS pathologies. In the context of this dichotomy, we summarize and discuss the current knowledge on the spatiotemporal physiology of macrophage subsets and microglia in the healthy and diseased CNS, and elaborate on factors regulating their behavior. In addition, the impact of macrophages present in lymphoid organs on CNS pathologies is defined. The prime focus of this review is on multiple sclerosis (MS), which is characterized by inflammation, demyelination, neurodegeneration, and CNS repair, and in which microglia and macrophages have been extensively scrutinized. On one hand, microglia and macrophages promote neuroinflammatory and neurodegenerative events in MS by releasing inflammatory mediators and stimulating leukocyte activity and infiltration into the CNS. On the other hand, microglia and macrophages assist in CNS repair through the production of neurotrophic factors and clearance of inhibitory myelin debris. Finally, we define how microglia and macrophage physiology can be harnessed for new therapeutics aimed at suppressing neuroinflammatory and cytodegenerative events, as well as promoting CNS repair. We conclude that microglia and macrophages are highly dynamic cells displaying disease stage and location-specific fates in neurological disorders. Changing the physiology of divergent phagocyte subsets at particular disease stages holds promise for future therapeutics for CNS pathologies.

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

“…Thus, we have chosen to use the broader terms "inflammatory" and "repair-promoting" (antiinflammatory) in lieu of M1 and M2 polarization status (27). As in other inflammatory diseases (7,28), the shift from the initially prevalent population of proinflammatory to antiinflammatory cells (29), and the subsequent prompt clearance of the proinflammatory population, may have a fundamental role in promoting tissue remodeling (resolution of the glial scar) and enhancing repair (remyelination, new synapse sprouting) (30)(31)(32) (Figure 9). We propose that this is the case in the second scenario, in which the phase rim disappears when enhancement resolves (here, we termed these lesions "centripetal lesions with transient rim").…”

Microglial Phenotypes and Functions in Multiple Sclerosis

“…Microglia, together with macrophages, are the most abundant immune cells in active MS lesions of the brain and spinal cord (Bogie et al 2014). Activated microglia are present during early and late MS stages (van der Valk and Amor 2009;Singh et al 2013).…”

Double Application of Translocator Protein Ligands and RAW Cells Inflammatory Milieu

“…Because the principal effector cells in neuroinflammatory and neuro-degenerative disorders are microglia, monocyte-derived macrophages, macrophages in the perivascular space, the choroid plexus and the meninges (Bogie et al, 2014), the use of the RAW cell line (derived from murine macrophages) was an appropriate choice for this study.…”