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

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

Immune Players in the CNS:The Astrocyte

<p>In the finely balanced environment of the central nervous system astrocytes, the most numerous cell type, play a role in regulating almost every physiological system. First found to regulate extracellular ions and pH, they have since been shown to regulate neurotransmitter levels, cerebral blood flow and energy metabolism. There is also growing evidence for an essential role of astrocytes in central immunity, which is the topic of this review. In the healthy state, the central nervous system is potently anti-inflammatory but under threat astrocytes readily respond to pathogens and to both sterile and pathogen-induced cell damage. In response, astrocytes take on some of the roles of immune cells, releasing cyto- and chemokines to influence effector cells, modulating the blood-brain barrier and forming glial scars. To date, much of the data supporting a role for astrocytes in immunity have been obtained from in vitro systems; however data from experimental models and clinical samples support the suggestion that astrocytes perform similar roles in more complex environments. This review will discuss some aspects of the role of astrocytes in central nervous system immunity.</p>