Heterogeneity of Microglial Activation in the Innate Immune Response in the Brain

By Carol A. Colton. Journal of Neuroimmune Pharmacology, 2009

891 citations recorded by the source corpus.

The immune response in the brain has been widely investigated and while many studies have focused on the proinflammatory cytotoxic response, the brain’s innate immune system demonstrates significant heterogeneity. Microglia, like other tissue macrophages, participate in repair and resolution processes after infection or injury to restore normal tissue homeostasis. This review examines the mechanisms that lead to reduction of self-toxicity and to repair and restructuring of the damaged extracellular matrix in the brain. Part of the resolution process involves switching macrophage functional activation to include reduction of proinflammatory mediators, increased production and release of anti-inflammatory cytokines, and production of cytoactive factors involved in repair and reconstruction of the damaged brain. Two partially overlapping and complimentary functional macrophage states have been identified and are called alternative activation and acquired deactivation. The immunosuppressive and repair processes of each of these states and how alternative activation and acquired deactivation participate in chronic neuroinflammation in the brain are discussed.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/9ce6c02b1a9a083c25f5875b87dd22c2e134fd27

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Citations in the corpus

Neuroinflammation Induces Neurodegeneration (2016, background): “Microglia in the state of alternative activation is called M2 phenotype and is associated with neuroprotection and is anti-inflammatory [71].”
Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. (2012, neutral): “Dependent on the stimuli in their local microenvironment microglia can be polarized to have distinct molecular phenotypes and effector functions (Colton, 2009).”
Nitric oxide and redox mechanisms in the immune response (2011, neutral): “TGF- [191–193].”
Microglial M1/M2 polarization and metabolic states (2016, background): “Based upon peripheral macrophage nomenclature, M1 and M2 polarization states of microglia have been proposed as a framework to evaluate the heterogeneity of responses (Colton, 2009; Mosser and Edwards, 2008) with recent evaluations suggesting a framework focused on the inducing stimuli (Martinez and”
Microglia in the TBI Brain: The Good, The Bad, And The Dysregulated (2015, background): “…adopt a ‘deactivated’M2c-like phenotype in response to IL-10, glucocorticoids, or uptake of apoptotic cells, and this phenotype appears to be involved in tissue remodeling and matrix deposition after inflammation has been downregulated (Colton, 2009; Gordon, 2003; Sica and Mantovani, 2012).”
Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases (2015, background): “Acquired deactivation is another state to alleviate acute inflammation and is induced primarily by uptake of apoptotic cells or exposure to the insult of antiinflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β) [18] [19] [23].”
Neuroinflammation and M2 microglia: the good, the bad, and the inflamed (2014, background): “activated microglia can exist broadly in two different states [6].”
Role of Microglia in Neurotrauma (2010, positive): “Described as an alternatively activated subset of microglia (M2), these cells have markers that can differentiate them from classically activated microglia (M1).(54,55) The M2 microglia are typically considered to be less inflammatory than M1 microglia; they are characterized by reduced NO productio”
Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro (2013, methodology): “Markers were characterised as M1, M2a or M2b based on previous reports (Mantovani et al., 2004; Martinez et al., 2009; Ransohoff and Perry, 2009; Colton and Wilcock, 2010).”
Alternatively activated microglia and macrophages in the central nervous system. (2015, background): “…by the expression of antiflammatory molecules as Ym1, Fizz1, insulin growth factor in the M2a phenotype or CXCL13 and suppressor of cytokine naling 3 in the M2c phenotype (Chhor et al., 2013; Colton, 2009; vid and Kroner, 2011; Fenn et al., 2012; Hu et al., 2012; Varnum d Ikezu, 2012).”