The microglial "activation" continuum: from innate to adaptive responses
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BioMed Central
Open Access
Review
The microglial "activation" continuum: from innate to adaptive responses Terrence Town*1,2, Veljko Nikolic2 and Jun Tan*2 Address: 1Section of Immunobiology, Yale University School of Medicine, 300 Cedar St., New Haven, CT 06520-8011, USA and 2Neuroimmunology Laboratory, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida, 3515 E. Fletcher Ave., Tampa, FL 33613, USA Email: Terrence Town* - [email protected]; Veljko Nikolic - [email protected]; Jun Tan* - [email protected] * Corresponding authors
Published: 31 October 2005 Journal of Neuroinflammation 2005, 2:24
doi:10.1186/1742-2094-2-24
Received: 24 October 2005 Accepted: 31 October 2005
This article is available from: http://www.jneuroinflammation.com/content/2/1/24 © 2005 Town et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
brainmicrogliainnate immunityadaptive immunityToll-like receptorinflammationencephalitismyelinamyloidvaccineimmunotherapy
Abstract Microglia are innate immune cells of myeloid origin that take up residence in the central nervous system (CNS) during embryogenesis. While classically regarded as macrophage-like cells, it is becoming increasingly clear that reactive microglia play more diverse roles in the CNS. Microglial "activation" is often used to refer to a single phenotype; however, in this review we consider that a continuum of microglial activation exists, with phagocytic response (innate activation) at one end and antigen presenting cell function (adaptive activation) at the other. Where activated microglia fall in this spectrum seems to be highly dependent on the type of stimulation provided. We begin by addressing the classical roles of peripheral innate immune cells including macrophages and dendritic cells, which seem to define the edges of this continuum. We then discuss various types of microglial stimulation, including Toll-like receptor engagement by pathogen-associated molecular patterns, microglial challenge with myelin epitopes or Alzheimer's β-amyloid in the presence or absence of CD40L co-stimulation, and Alzheimer disease "immunotherapy". Based on the wide spectrum of stimulus-specific microglial responses, we interpret these cells as immune cells that demonstrate remarkable plasticity following activation. This interpretation has relevance for neurodegenerative/neuroinflammatory diseases where reactive microglia play an etiological role; in particular viral/bacterial encephalitis, multiple sclerosis and Alzheimer disease.
Introduction Microglia are somewhat enigmatic central nervous system (CNS) cells that have been traditionally regarded as CNS macrophages (MΦs). They represent about 10% on average of the adult CNS cell population [1]. In mice, microgli
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