Abstract
The complement system, an effector arm of the innate immune system that plays a critical role in tissue inflammation, the elimination of pathogens and the clearance of dead cells and cell debris, has emerged as a regulator of many processes in the central nervous system, including neural cell genesis and migration, control of synapse number and function, and modulation of glial cell responses. Complement dysfunction has also been put forward as a major contributor to neurological disease. Astrocytes are neuroectoderm-derived glial cells that maintain water and ionic homeostasis, and control cerebral blood flow and multiple aspects of neuronal functioning. By virtue of their expression of soluble as well as membrane-bound complement proteins and receptors, astrocytes are able to both send and receive complement-related signals. Here we review the current understanding of the multiple functions of the complement system in the central nervous system as they pertain to the modulation of astrocyte activity, and how astrocytes use the complement system to affect their environment in the healthy brain and in the context of neurological disease.
Highlights
By virtue of its ability to sense and rapidly respond to diverse danger signals, the complement system plays an essential role in the innate immune responses and constitutes the first line of defense against pathogens such as bacteria, viruses, mycoplasma, fungi, and protozoa
Through a number of complement receptors expressed on their cell membrane, astrocytes are well equipped to sense the level of complement activation in their vicinity, as well as receive and respond to complement-derived signals sent by other cells
There is evidence pointing to the role of astrocyte-derived C3 and neuronal C3a receptor (C3aR) signaling in synaptic plasticity and maintaining normal dendritic extension [17]
Summary
By virtue of its ability to sense and rapidly respond to diverse danger signals, the complement system plays an essential role in the innate immune responses and constitutes the first line of defense against pathogens such as bacteria, viruses, mycoplasma, fungi, and protozoa. Whereas the functions of the complement system in the elimination of pathogens, antigen-antibody complexes, dead cells and tissue debris, and their involvement in the regulation of the responses mediated by antibodies and cells of the adaptive immune system have been well recognized for many decades, the homeostatic and non-immune tasks of the complement proteins only recently began to be unraveled. Astrocytes are a major source of the complement system proteins, of the third complement component (C3), and they stand out as a very prominent player or effector in many of the complementmediated processes. Through a number of complement receptors expressed on their cell membrane, astrocytes are well equipped to sense the level of complement activation in their vicinity, as well as receive and respond to complement-derived signals sent by other cells
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