The Role of Microglia and Macrophages in CNS Homeostasis, Autoimmunity, and Cancer

Abstract

Macrophages are major cell types of the immune system, and they comprise both tissue-resident populations and circulating monocyte-derived subsets. Here, we discuss microglia, the resident macrophage within the central nervous system (CNS), and CNS-infiltrating macrophages. Under steady state, microglia play important roles in the regulation of CNS homeostasis through the removal of damaged or unnecessary neurons and synapses. In the face of inflammatory or pathological insults, microglia and CNS-infiltrating macrophages not only constitute the first line of defense against pathogens by regulating components of innate immunity, but they also regulate the adaptive arms of immune responses. Dysregulation of these responses contributes to many CNS disorders. In this overview, we summarize the current knowledge regarding the highly diverse and complex function of microglia and macrophages during CNS autoimmunity—multiple sclerosis and cancer—malignant glioma. We emphasize how the crosstalk between natural killer (NK) cells or glioma cells or glioma stem cells and CNS macrophages impacts on the pathological processes. Given the essential role of CNS microglia and macrophages in the regulation of all types of CNS disorders, agents targeting these subsets are currently applied in preclinical and clinical trials. We believe that a better understanding of the biology of these macrophage subsets offers new exciting paths for therapeutic intervention.

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

“…Microglia and infiltrating macrophages are both derived from the myeloid lineage and they perform a variety of functions in order to respond to CNS pathological insults and to maintain CNS homeostasis [8]. Proper activation and function of these cells are required in order to elicit innate and adaptive immune responses.…”

“…Known as resident macrophages of the CNS, microglial cells perform a multitude of important functions during homeostasis and disease. In healthy brains, microglia are found in their ramified morphology, functioning as sentinels by sampling their surroundings and maintaining homeostasis through the clearance of cellular debris [5][6][7][8]. In this state, microglia can be referred to as homeostatic microglia [9].…”

Macrophages: The Potent Immunoregulatory Innate Immune Cells

“…The chronic up-regulation of CCR2, CCL2, CCL3, CCL4, and CCL22 stimulates the process of macrophage accumulation at the sites of the brain affected during EAE [179,180]. Both M1 and M2 macrophages play a crucial role in the pathogenesis of EAE or MS [180,181]. Macrophages also play a very important role in the pathogenesis of rheumatoid arthritis (RA) by secreting various pro-inflammatory cytokines, controlling the generation and function of regulatory T cells (Tregs) via binding and release of transforming growth factor-β (TGFβ), and their therapeutic targeting proves beneficial to the patients [182][183][184][185].…”

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

“…Elevated levels of TSPO are associated with gliosis in neuropsychiatric diseases [14][15][16][17]. Gliosis involves a transformation of microglia and astroglia from surveillance functions to inflammatory and/or repair roles, to respond to various types of brain injury [18] changing morphology from branched to globular, with a large increase in cell volume, while migrating to and engulfing the site of insult.…”