Glial cells and the immune response
The potential importance of glial cells in human cognition is emphasised in the previous article in this thread. Human glial cells are recognised to play many other important roles however, for example in the regulation of innate immune responses in the central nervous system. Both glial cells and neurons express toll-like receptors (TLRs). However, glial cells are much more abundant than neurons. TLRS are pattern recognition receptors, which recognise conserved molecular motifs in pathogens and are central to innate immunity. The TLR family recognise conserved motifs known as pathogen-associated molecular patterns (PAMPs). There are currently ten known human TLRs. Recognition of PAMPs by TLRs results in signalling cascades with activation of transcription factors and cellular responses including the production of inflammatory mediators such as interferons (IFNs) and cytokines. This helps initiate the innate immune response.
In the CNS glial cells, including microglia, astrocytes and oligodendrocytes, act as sensors for neuroinflammation. Activation of TLRs on glial cells results in activation of pro-inflammatory mediators and hence in increased expression of membrane pores that allow ATP release and Ca(2+) influx. As a consequence of this, activated glial cells release ATP and glutamate, affecting myelinisation, neuronal development, and survival. It is hypothesised that occurrence of inflammatory responses in pregnancy could pre-dispose children to psychiatric and neurological disorders such as autism and schizophrenia. It has also been suggested that innate immune responses may be implicated in lowering seizure threshold in experimental models of epilepsy. A study from the University of Colorado in the USA implicated TLR4 signalling on glial cells as a potential contributor to acute seizures, which could be ameliorated by pre-application of interleukin-1 receptor antagonist. They suggested that inhibition of TLR4 signalling on glial cells could be a potential therapeutic target in human seizure disorders such as epilepsy. However, TLRs on glial cells may also recognise endogenous molecules released from damaged tissue, suggesting that TLRs on glial cells may be involved in initiation of an inflammatory response to tissue damage in the nervous system important in repair, for example in strokes and peripheral nerve injuries.
Sources
AGUIRRE, A. et al., 2013. Possible Involvement of TLRs and Hemichannels in Stress-Induced CNS Dysfunction via Mastocytes, and Glia Activation. Mediators of inflammation, 2013, pp. 893521-893521
LEE, H. et al., 2013. Toll-like receptors: sensor molecules for detecting damage to the nervous system. Current Protein & Peptide Science, 14(1), pp. 33-42
MAJDE, J.A., 2010. Neuroinflammation resulting from covert brain invasion by common viruses - a potential role in local and global neurodegeneration. Medical hypotheses, 75(2), pp. 204-213
RODGERS, K.M. et al., 2009. The cortical innate immune response increases local neuronal excitability leading to seizures. Brain: A Journal Of Neurology, 132, pp. 2478-2486
The potential importance of glial cells in human cognition is emphasised in the previous article in this thread. Human glial cells are recognised to play many other important roles however, for example in the regulation of innate immune responses in the central nervous system. Both glial cells and neurons express toll-like receptors (TLRs). However, glial cells are much more abundant than neurons. TLRS are pattern recognition receptors, which recognise conserved molecular motifs in pathogens and are central to innate immunity. The TLR family recognise conserved motifs known as pathogen-associated molecular patterns (PAMPs). There are currently ten known human TLRs. Recognition of PAMPs by TLRs results in signalling cascades with activation of transcription factors and cellular responses including the production of inflammatory mediators such as interferons (IFNs) and cytokines. This helps initiate the innate immune response.
In the CNS glial cells, including microglia, astrocytes and oligodendrocytes, act as sensors for neuroinflammation. Activation of TLRs on glial cells results in activation of pro-inflammatory mediators and hence in increased expression of membrane pores that allow ATP release and Ca(2+) influx. As a consequence of this, activated glial cells release ATP and glutamate, affecting myelinisation, neuronal development, and survival. It is hypothesised that occurrence of inflammatory responses in pregnancy could pre-dispose children to psychiatric and neurological disorders such as autism and schizophrenia. It has also been suggested that innate immune responses may be implicated in lowering seizure threshold in experimental models of epilepsy. A study from the University of Colorado in the USA implicated TLR4 signalling on glial cells as a potential contributor to acute seizures, which could be ameliorated by pre-application of interleukin-1 receptor antagonist. They suggested that inhibition of TLR4 signalling on glial cells could be a potential therapeutic target in human seizure disorders such as epilepsy. However, TLRs on glial cells may also recognise endogenous molecules released from damaged tissue, suggesting that TLRs on glial cells may be involved in initiation of an inflammatory response to tissue damage in the nervous system important in repair, for example in strokes and peripheral nerve injuries.
Sources
AGUIRRE, A. et al., 2013. Possible Involvement of TLRs and Hemichannels in Stress-Induced CNS Dysfunction via Mastocytes, and Glia Activation. Mediators of inflammation, 2013, pp. 893521-893521
LEE, H. et al., 2013. Toll-like receptors: sensor molecules for detecting damage to the nervous system. Current Protein & Peptide Science, 14(1), pp. 33-42
MAJDE, J.A., 2010. Neuroinflammation resulting from covert brain invasion by common viruses - a potential role in local and global neurodegeneration. Medical hypotheses, 75(2), pp. 204-213
RODGERS, K.M. et al., 2009. The cortical innate immune response increases local neuronal excitability leading to seizures. Brain: A Journal Of Neurology, 132, pp. 2478-2486
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