Toll-like receptors in the pathogenesis of neuroinflammation

  • V. Kumar
    Correspondence
    Children Health Clinical Unit, School of Clinical Medicine, Faculty of Medicine, Mater Research, University of Queensland, ST Lucia, Brisbane, Queensland 4078, Australia.
    Affiliations
    Children Health Clinical Unit, School of Clinical Medicine, Faculty of Medicine, Mater Research, University of Queensland, ST Lucia, Brisbane, Queensland 4078, Australia

    School of Biomedical Sciences, Faculty of Medicine, University of Queensland, ST Lucia, Brisbane, Queensland 4078, Australia
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      Highlights

      • TLRs are crucial PRRs to recognize both intracellular and extracellular PAMPs or DAMPs.
      • TLRs are also expressed by brain microglia, astrocytes, oligodendrocytes, and neurons.
      • Activation of TLRs plays a crucial role in generating neuroinflammatory immune response.
      • Both MyD88-dependent and MyD88-independent TLR signaling pathways generate neuroinflammation.
      • Neuroinflammation is involved in both sterile (stroke, AD, PD, and MS) and infectious diseases of the brain.

      Abstract

      Toll-like receptors (TLRs) are discovered as crucial pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs). Later studies showed their involvement in the recognition of various damage/danger-associated molecular patterns (DAMPs) generated by host itself. Thus, TLRs are capable of recognizing wide-array of patterns/molecules derived from pathogens and host as well and initiating a proinflammatory immune response through the activation of NF-κB and other transcription factors causing synthesis of proinflammatory molecules. The process of neuroinflammation is seen under both sterile and infectious inflammatory diseases of the central nervous system (CNS) and may lead to the development of neurodegeneration. The present article is designed to highlight the importance of TLRs in the pathogenesis of neuroinflammation under diverse conditions. TLRs are expressed by various immune cells present in CNS along with neurons. However out of thirteen TLRs described in mammals, some are present and active in these cells, while some are absent and are described in detail in main text. The role of various immune cells present in the brain and their role in the pathogenesis of neuroinflammation depending on the type of TLR expressed is described. Thereafter the role of TLRs in bacterial meningitis, viral encephalitis, stroke, Alzheimer's disease (AD), Parkinson's disease (PD), and autoimmune disease including multiple sclerosis (MS) is described. The article is designed for both neuroscientists needing information regarding TLRs in neuroinflammation and TLR biologists or immunologists interested in neuroinflammation.

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