Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

TY - JOUR

T1 - Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

AU - Li, Lun

AU - Acioglu, Cigdem

AU - Heary, Robert F.

AU - Elkabes, Stella

N1 - Publisher Copyright: © 2020 The Authors

PY - 2021/1

Y1 - 2021/1

N2 - Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.

AB - Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes and microglia are the principal cells that mediate innate immunity in the CNS. Pattern recognition receptors (PRRs), expressed by astrocytes and microglia, sense pathogen-derived or endogenous ligands released by damaged cells and initiate the innate immune response. Toll-like receptors (TLRs) are a well-characterized family of PRRs. The contribution of microglial TLR signaling to CNS pathology has been extensively investigated. Even though astrocytes assume a wide variety of key functions, information about the role of astroglial TLRs in CNS disease and injuries is limited. Because astrocytes display heterogeneity and exhibit phenotypic plasticity depending on the effectors present in the local milieu, they can exert both detrimental and beneficial effects. TLRs are modulators of these paradoxical astroglial properties. The goal of the current review is to highlight the essential roles played by astroglial TLRs in CNS infections, injuries and diseases. We discuss the contribution of astroglial TLRs to host defense as well as the dissemination of viral and bacterial infections in the CNS. We examine the link between astroglial TLRs and the pathogenesis of neurodegenerative diseases and present evidence showing the pivotal influence of astroglial TLR signaling on sterile inflammation in CNS injury. Finally, we define the research questions and areas that warrant further investigations in the context of astrocytes, TLRs, and CNS dysfunction.

KW - Alzheimer's disease

KW - Amyotrophic lateral sclerosis

KW - Astrogliosis

KW - Brain injury

KW - COVID-19

KW - Cytokines

KW - Infection

KW - Neuroinflammation

KW - Neuroprotection

KW - Parkinson's disease

KW - Pattern recognition receptors

KW - SARS-CoV-2

KW - Spinal cord injury

UR - http://www.scopus.com/inward/record.url?scp=85094876264&partnerID=8YFLogxK

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U2 - 10.1016/j.bbi.2020.10.007

DO - 10.1016/j.bbi.2020.10.007

M3 - Review article

C2 - 33039660

SN - 0889-1591

VL - 91

SP - 740

EP - 755

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

ER -