Functional plasticity of microglia: A review

Abstract

The present review summarizes recently acquired data in vivo, which support a role of CNS microglia as a source of defense cells in the CNS capable of carrying out certain immune functions autonomously. We have kept the following discussion restricted to microglial cells and have not included work on the immunological functions of astrocytes, which has been recently reviewed elsewhere (Fontana et al.: Immunological Reviews 137:3521-3527, 1987). Resting microglia are scattered uniformly throughout the CNS forming a network of potential immunoeffector cells, which can be activated by stimuli ranging from peripheral nerve injury over viral infections to direct mechanical brain trauma. The term "activated microglia" is used here to describe proliferating cells that demonstrate changes in their immunophenotype but have not undergone transformation into brain macrophages. Such a transformation can be stimulated by neuronal death but not by sublethal neuronal injury. Microglia may function as antigen-presenting cells and may thus represent the effector cell responsible for the recruitment of lymphocytes to the brain resulting in an inflammatory reaction. The recent developments in the understanding of microglial cell function may lead to a redefinition of the often cited "immune privilege" of the brain.

Role of microglia in CNS inflammation

“…The term ''activated microglial cells'' was formally introduced when it became apparent that intrinsic (resident) microglia are capable of up-regulating certain molecules, including several that are not normally expressed in the CNS [12][13][14]. Such chameleon-like behaviour illustrates the now well-recognized phenotypic and functional plasticity of microglia [15]. However there remain problems distinguishing microglia, especially after activation, from bone marrow-derived macrophages.…”

Post-traumatic inflammation following spinal cord injury

“…The term 'activated microglia' is used to describe proliferating nonphagocytic cells that demonstrate changes in their immunophenotype and their morphology, but have not undergone transformation into brain phagocytic macrophages. 7,65 However, it is not possible to reliably distinguish activated microglia from invading peripheral bloodborn macrophages using immunohistochemistry alone. The morphological diversity of microglia is indicative of functional heterogeneity.…”

“…The morphological diversity of microglia is indicative of functional heterogeneity. 2,36,64,65 For example, the concomitant increase in expression of major histocompatibility complex (MHC) antigen class II is only seen in a subpopulation of microglia with increased OX42 immunoreactivity. 7 The OX42 antibody recognizes complement CD 11 (C3b receptor) expressed by resting and activated resident microglia as well as by peripheral macrophages.…”

Microglia/Macrophages Migrate through Retinal Epithelium Barrier by a Transcellular Route in Diabetic Retinopathy

“…5 Microglial cells, the main resident sentinel immune cells, are located in the inner part of the retina, around vessels in the healthy retina. [7][8][9][10][11][12] These cells become activated and migrate in the subretinal space in several retinopathies such as diabetic retinopathy, 13,14 age-related macular degeneration, 15 and aging. 5,16,17 The activation of microglia induced by hyperglycemia has been associated with the early development of DR.…”